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Skin Remodeling Copper Peptides
SRCPs activate the skin's anti-proteases TIMP-1 and TIMP-2 - Simeon, Emonard, Hornebeck & Maquart,The tripeptide-copper complex GHK-Cu stimulates matrix metalloproteinases 2 expression by fibroblast cultures
Life Sci 2000 Sep 22;67(18):2257-65.
Retinoic acid increases TGF-beta - McCormack, M., Nowak KC, Koch, J, The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model., Arch Facial Plast Surg 2001; 3: 28-32.
Copper Peptide Complexes are potent activators of metalloproteinases - Alain, Monier, Emonard, Gillery, Birembaut, Homebeck and Maquart, Expression and activation of matrix metalloproteinases in wounds: Modulation by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-cu2+, J. Invest. Dermat. 112: 957-964.
Maquart FX; Simeon A; Pasco S; Monboisse JC, Regulation de l'activite cellulaire par la matrice extracelulaire: le concept de matrikines, J Soc Biol 1999;193(4-5):423-8.
Simeon, Monier, Emonard, Gillery, Birembaut, Homebeck and Maquart,Expression and activation of matrix metalloproteinases in wounds: Modulation by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-cu2+, J. Invest. Dermat. 112: 957-964.
Abulghani, Shirin, Morales-Tapia, Sherr, Solodkina, Robertson, and Gottlieb, J. Invest. Derm. 110(4), page 686, 1998.
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A mixture of cholesterol, ceramides and free fatty acids was shown to accelerate repair of the skin's uppermost layer - Zterstein et al, 1997.
This may be the reason for the positive actions of emu oil on human skin - Zemtsov et al, 1996.
A study of emu oil found strong anti-inflammatory effects - Lopez et al, 1999.
Emu oil applied 2 days after injury aided the healing process - Politis and Dmytrowich, 1998.
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Simeon, Emonard, Hornebeck & Maquart, The tripeptide-copper complex GHK-Cu stimulates matrix metalloproteinases 2 expression by fibroblast cultures, Life Sci 2000 Sep 22;67(18):2257-65.
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Garland, Cedric F., et al. Could sunscreens increase melanoma risk? American Journal of Public Health, Vol. 82, No. 4, April 1992, pp. 614-15.
Ainsleigh, H. Gordon. Beneficial effects of sun exposure on cancer mortality. Preventive Medicine, Vol. 22, February 1993, pp. 132-40.
Garland, Cedric F. et al. Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. Journal of the National Cancer Institute, Vol. 86, No. 10, May 18, 1994, pp. 798-80.
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Abstract of First Paper Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14187-14192.
Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid A{beta} production in APP23 transgenic mice.
Bayer TA, Schafer S, Simons A, Kemmling A, Kamer T, Tepests R, Eckert A, Schussel K, Eikenberg O, Sturchler-Pierrat C, Abramowski D, Staufenbiel M, Multhaup G.
Department of Psychiatry, Division of Neurobiology, University of the Saarland Medical Center, D-66421 Homburg, Germany.
The Cu-binding beta-amyloid precursor protein (APP), and the amyloid Abeta peptide have been proposed to play a role in physiological metal regulation. There is accumulating evidence of an unbalanced Cu homeostasis with a causative or diagnostic link to Alzheimer's disease. Whereas elevated Cu levels are observed in APP knockout mice, APP overexpression results in reduced Cu in transgenic mouse brain. Moreover, Cu induces a decrease in Abeta levels in APP-transfected cells in vitro. To investigate the influence of bioavailable Cu, transgenic APP23 mice received an oral treatment with Cu-supplemented sucrose-sweetened drinking water (1). Chronic APP overexpression per se reduced superoxide dismutase 1 activity in transgenic mouse brain, which could be restored to normal levels after Cu treatment (2). A significant increase of brain Cu indicated its bioavailability on Cu treatment in APP23 mice, whereas Cu levels remained unaffected in littermate controls (3). Cu treatment lowered endogenous CNS Abeta before a detectable reduction of amyloid plaques. Thus, APP23 mice reveal APP-induced alterations linked to Cu homeostasis, which can be reversed by addition of dietary Cu.
Abstract of Second Paper Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14193-14198
In vivo reduction of amyloid-{beta} by a mutant copper transporter.
Phinney AL, Drisaldi B, Schmidt SD, Lugowski S, Coronado V, Liang Y, Horne P, Yang J, Sekoulidis J, Coomaraswamy J, Chishti MA, Cox DW, Mathews PM, Nixon RA, Carlson GA, George-Hyslop PS, Westaway D.
Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2.
Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-beta (Abeta) peptide. To explore this relationship in vivo, toxic-milk (txJ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Abeta deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive txJ mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Abeta levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS Abeta at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide.
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Ingredients
Journal of Agricultural Food Chemistry, February 2002, pages 840–845.
Skin Research and Technology, November 2006, pages 241–246.
Journal of Ethnopharmacology, December 1999, pages 3–37; Free-Radical Biology and Medicine, January 2000, pages 261–265; and British Journal of Dermatology, October 2001, pages 535–545.
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British Journal of Dermatology, March 1998, pages 467–476.
Zemtsov et al, 1996. Lopez et al, 1999. Politis and Dmytrowich, 1998.
American Journal of Contact Dermatitis, September 2000, pages 165–169; and Acta Dermato-Venereologica, November 1999, pages 418–421.
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Escedilrefogbrevelu, M, Seyhan, M, Gül, M, Parlakpinodotnar, H, Batçinodotogbrevelu, K, Uyumlu, B, Potent therapeutic effect of melatonin on aging skin in pinealectomized rats. Journal of Pineal Research, Volume 39, Number 3, October 2005 , pp. 231-237(7).
Publisher: Blackwell Publishing
Abstract:
It is generally agreed that one of the major contributors to skin aging is reactive oxygen species. As organisms reach advanced age, free radical generation increases and the activity of tissue antioxidant enzyme system decreases. Melatonin is an antioxidant and free radical scavenger. The present study was first aimed to determine the morphometric and biochemical changes caused by long-term pinealectomy in order to investigate the role of melatonin as skin architecture. Secondly, the effect of exogenous melatonin administration on these changes was determined. Rats were pinealectomized or sham operated (control) for 6 months. Half of the pinealectomized rats were treated with 4 mg/kg melatonin during the last month of the experiment. Pinealectomy resulted in important morphometric and biochemical changes in the back, abdominal and thoracic skin. The thickness of epidermis and dermis and the number of dermal papillae and hair follicles were reduced. Melatonin administration to pinealectomized rats significantly improved these alterations in all body areas (P < 0.005). On the contrary, in pinealectomized rats the levels of antioxidant enzymes, catalase and glutathione peroxidase were decreased. Melatonin restored the levels of these enzymes. The pinealectomy-induced increases in lipid peroxidation in the abdominal and thoracic skin were significantly reduced by melatonin treatment (P < 0.005 and 0.01 respectively). These results suggest that melatonin is highly efficient anti-aging factor and, as melatonin levels decrease with age, melatonin treatment may reduce age-related skin changes.
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Bangha E, et al. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point. Dermatology 195:248-52, 1997.
Carcinogenesis, November 2000, pages 2085–2090; and Journal of Dermatological Science, March 2000, Supplemental, pages S45–S50.
Free Radical Biology and Medicine, February 2001, pages 393–402.
Skin Therapy Letter, 1997, volume 2, number 5.
Fitoterapia, July 2002, page 336; Phytotherapy Research, March 2001, pages 174–176; and Drug Metabolism and Drug Interaction, 2000, volume 17, issue 1-4, pages 211–235.
Journal of Nutrition, February 2001, pages 369S–373S.
Current Problems in Dermatology, 2001, volume 29, pages 26–42; Free Radical Biology and Medicine, May 1997, pages 761–769; Journal of Nutrition, February 2001, pages 369S–373S; and International Journal of Radiation Biology, June 1999, pages 747–755.
Pointing to the significance of vitamin E for skin is an article in the Journal of Molecular Medicine (January 1995, pages 7–17), which states: “More than other tissues, the skin is exposed to numerous environmental chemical and physical agents such as ultraviolet light causing oxidative stress [free-radical damage]. In the skin this results in several short- and long-term adverse effects such as erythema [redness], edema [swelling], skin thickening, wrinkling, and an increased incidence of skin cancer…. Vitamin E is the major naturally occurring lipid-soluble … antioxidant protecting skin from the adverse effects of oxidative stress including photoaging [sun damage]. Many studies document that vitamin E occupies a central position as a highly efficient antioxidant, thereby providing possibilities to decrease the frequency and severity of pathological events in the skin.”
Biofactors, November 2005, pages 179–185. Journal of Cosmetic Dermatology, March 2006, pages 30–38.
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Darbre PD, Aljarrah A, Miller WR, Coldham NG, Sauer MJ, Pope GS, Concentrations of parabens in human breast tumours. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.
Harvey, Philip W.; Darbre, Philippa. Endocrine disrupters and human health: Could estrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women? A review of evidence and call for further research. Journal of Applied Toxicology (2004), 24(3), 167-176.
Parabens in deodorants and antiperspirants linked to breast cancer (NICNAS Search page)
Golden, Robert; Gandy, Jay; Vollmer, Guenter, A Review of the Endocrine Activity of Parabens and Implications for Potential Risks to Human Health. Critical Reviews in Toxicology (2005), 35(5), 435-458.
The American Cancer Society Antiperspirants and Breast Cancer Risk
Byford JR, Shaw LE, Drew MG, Pope GS, Sauer MJ, Darbre PD. Oestrogenic activity of parabens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol. 2002 Jan;80(1):49-60.
http://www.cosmeticsandtoiletries.com/newsletter/18725064.html?index=18
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von Woedtke T; Schluter B; Pflegel P; Lindequist U; Julich WD. Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained. Institute of Pharmacy, Ernst Moritz Arndt University, Greifswald, Germany. Pharmazie (1999) June;54(6):452-6.
Cosmetics & Toiletries, January 2005, page 22.
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Menopause, May–June 2004, pages 281–289.
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Yohini Appa, PhD; Neutrogena Corporation, Los Angeles, CA; Thomas Stephens, PhD; TJ Stephens & Associates, Inc, Dallas, TX; Sylvia Barkovic; Neutrogena Corporation, Los Angeles, CA; Mary Beth Finkey, MS, A Clinical Evaluation of a Copper-Peptide Containing Liquid Foundation and Cream Concealer Designed for Improving Skin Condition, Neutrogena Corporation, Los Angeles, CA.
James J Leyden, MD; University of Pennsylvania, Philadelphia, PA; Gary Grove, PhD; KGL, Inc/Skin Study Center, Broomall, PA; Sylvia Barkovic, The Effect of Tripeptide to Copper Ratio in Two Copper Peptide Creams on Photoaged Facial SkinNeutrogena Corporation, Los Angeles, CA; Yohini Appa, PhD; Neutrogena Corporation, Los Angeles, CA.
James J Leyden, MD; University of Pennsylvania, Philadelphia, PA; Thomas Stephens, PhD; Thomas J Stephens & Associates, Inc, Dallas, TX; Mary Beth Finkey, MS, Skin Care Benefits of Copper Peptide Containing Facial Cream. Neutrogena Corporation, Los Angeles, CA; Sylvia Barkovic; Neutrogena Corporation, Los Angeles, CA.
James J Leyden, MD; University of Pennsylvania, Philadelphia, PA; Thomas Stephens, PhD; Thomas J Stephens & Associates, Inc, Dallas, TX; Mary Beth Finkey, MS, Skin Care Benefits of Copper Peptide Containing Eye Creams. Neutrogena Corporation, Los Angeles, CA; Sylvia Barkovic; Neutrogena Corporation, Los Angeles, CA.
Thierry Oddos, PhD, Johnson & Johnson Consumer, Val de Reuil, France; Aurelie Jumeau-Lafond, Requirement of Copper and Tripeptide Glycyl-L-Histidyl-L-Lysine (GHK) Complex Formation for Collagen Synthesis Activity in Normal Human Dermal Fibroblasts. Johnson & Johnson Consumer, Val de Reuil, France; Gerd Ries, PhD; Johnson & Johnson, Dusseldorf, Germany
Pickart US Patent 4,760,051 Compositions containing glycyl-1-histidyl-1-lysine copper(II) enhance the wound healing process without evoking an antigenic response.
Pickart Iamin: A Human Growth Factor with Multiple Wound Healing Properties. in Biology of Copper Complexes, Clifton, NJ, 1987, pp. 273-285.
Perez-Meza et al, International Journal of Cosmetic Surgery, Vol. 6, 1998, pp 80-84.
Hitzig,G. Enhanced healing and growth in hair transplantation using copper peptides, Cosmetic Dermatol 2000 (June) ; 13, 18-21.
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Downey, Larrabee, Voci and Pickart, Acceleration of wound healing using glycyl-histidyl-lysine copper (II), Virginia Mason Research Center) Surg. Forum 573-575, 1985.
Pickart, Downey, Lovejoy and Weinstein, Gly-l-his-l-lys copper(II) - A human growth factor with superoxide dismutase-like and wound healing activities (University of Washington) In: Superoxide and Superoxide Dismutase (Elsevier, 1986) pp.555-558.
Pickart, Iamin: A human growth factor with multiple wound healing properties. Biology of Copper Complexes Plenum Press 1987, pp.273-282.
Pickart and Lovejoy, Biological activity of human plasma copper-binding growth factor glycyl-L-histidyl-L-lysine. Methods Enzymol 1987;147:314-28.
Counts, D, Hill E, Turner-Beatty M, Grotewiel M, Fosha-Thomas S, Pickart L. Effect of lamin on full thickness wound healing. Fed Am Soc Exp Biol 1992; A1636.
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Swaim SF, Vaughn DM, Kincaid SA, Morrison NE, Murray SS, Woodhead MA, Hoffman C.E, Wright JC, Kammerman JR, Effect of locally injected medications on healing of pad wounds in dogs. College of Veterinary Medicine, Auburn University, AL, USA, Am J Vet Res 1996 Vol. 57, 394-9
Swaim, Bradley, Spano, McGuire and Hoffman, Evaluation of multipeptide copper complex medications on open wound healing in dogs. (College of Veterinary Medicine, Auburn University, AL, USA) J Amer Ani Hos Assoc. 29, 519-525, 1993.
Aupaix, Maquart, Salagnac, Pickart, Gillery, Borel and Kalis J, Effects of the tripeptide glycyl-l-histidyl-l-lysine copper(II) on healing. Clinical and biochemical correlations. Invest Derm 94:390, 1990.
Fish S, Katz I, Hien NR, Briden ME, Johnson JA, Patt, L, Evaluation of glycyl-1-histidyl-1-lysine copper complex in acute wound healing. Wounds 1991, 3:171-177.
Ehrlich, Stimulation of skin healing in immunosuppressed rats (Harvard Medical School, Boston, USA) Presented at Symposium on collagen and skin repair Reims, France Sept. 12-13 1991.
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Massey P, Patt L, D'Aoust JC, The effects of glycyl-l-histidyl-l-lysine copper chelate on the healing of diabetic ulcers, Wounds 4:21-28, 1992.
Mulder, Patt, Sanders, Rosenstock, Altman, Hanley, Duncan, Enhanced healing of ulcers in patients with diabetes by topical treatment of glycyl-l-histidyl-l-lysine. Wound Rep Reg 2:259-269, 1994.
Schmidt, Resser, Sims, Mullins and Smith, The combined effects of glycyl-l-histidyl-l-lysine copper (II) on the healing of linear incision wounds. (University of Akron, Ohio, USA) Wounds 6, 62-67, 1994.
Buffoni, Pino and Dal Pozzo, Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts. (Department of Pharmacology, University of Florence, Firenze, Italy) Arch Int Pharmacodyn Ther 1995 330(3):345-60.
Pickart, US Patent 5,382,431 Tissue protective and regenerative compositions.
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Zhai, Chang, Singh, and Maibach, In vivo nickel contact dermatitis: human model for topical therapeutics. (University of California, San Francisco, USA) Contact Dermatitis Vol. 40, pp. 205-208, 1999.
Zhai, Poblete, and Maibach, Stripped skin model to predict irritation potential of topical agents in vivo in man. (University of California, San Francisco, USA) International Journal of Dermatology, Volume 37, pages 386-389, 1998.
Zhai, Leow, and Maibach, Sodium lauryl sulfate damaged skin in vivo in man: a water barrier repair model. (University of California, San Francisco, USA) Skin Research and Technology, Volume 4, pages 24-27, 1998.
Zhai, Leow, and Maibach, Human barrier recovery after acute acetone perturbation: an irritant dermatitis model. (University of California, San Francisco, USA) Clinical and Experimental Dermatology, Volume 23, pages 11-13, 1998.
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Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak A.M, Swaim SF, Vangilder J, Lee-Ambrose L, Martin FG, The effect of topical tripeptide-copper complex on healing of ischemic open wounds, Vet Surg. 2003 Nov-Dec;32(6):515-23.
Arul V, Gopinath D, Gomathi K, Jayakumar R. Biotinylated GHK peptide incorporated collagenous matrix: A novel biomaterial for dermal wound healing in rats. Biomed Mater Res B Appl Biomater. 2005 May;73(2):383-91.
Pickart, US Patent 4,665,054 New glycyl-L-histidyl-L-lysine copper derivatives of improved resistance to proteolytic enzymes and better fat solubility for use in inhibiting thromboxane production and enhancing wound healing.
Pickart, US Patent 4,760,051 Compositions containing glycyl-1-histidyl-1-lysine copper(II) enhance the wound healing process without evoking an antigenic response.
Pickart, US Patent 4,810,693 Copper glycyl-L-histidyl-L-lysine complexes enhance the healing of wounds and sores.
Pickart, US Patent 4,877,770 New glycyl-histidyl-lysine ester copper complex compounds with anti-inflammatory and superoxide dismutase activity useful for enhancing wound healing.
Pickart, US Patent 4,937,230 Method for healing wounds in horses using a copper complex of Glycyl-L-Histidyl-L-lysine or derivatives on the affected area.
Pickart, US Patent 5,164,367 Compositions for accelerating wound healing in mammals containing cupric salt or complexes with amino acid or peptide.
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Maquart, Gillery, Monboisse, Pickart, Laurent and Borel, Glycyl-l-histidyl-l-lysine, a triplet from the a2 (I) chain of human type I collagen, stimulates collagen synthesis by fibroblast cultures. Ann. N.Y. Acad. Sci. 580:573-575, 1990.
Sage and Vernon, Regulation of angiogenesis by extracellular matrix: the growth and the glue. (University of Washington School of Medicine, Seattle, WA, USA) J Hypertens Suppl 1994 12(10):S145-52.
Poole and Zetter, Stimulation of rat peritoneal mast cell migration by tumor derived peptides. (Harvard Medical School) Cancer. Res. 43, 5857-5861, 1983.
Zetter, Rasmussen and Brown, An in vivo assay for chemoattractant activity. (Harvard University Medical School, Boston, MA, USA) Lab Invest 1985 53(3):362-8.
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Rabenstein, Robert and Hari, Binding of the growth factor glycyl-L-histidyl-L-lysine by heparin. (University of California at Riverside, USA) FEBS Lett 1995, 376, pp. 216-20.
Raju, Alessandri, Ziche and Gullino, Ceruloplasmin, copper ions, and angiogenesis. (National Cancer Institute, Bethesda, MD, USA) J Natl Cancer Inst 1982 69(5):1183-8.
Raju, Alessandri, Gullino, Characterization of a chemoattractant for endothelium induced by angiogenesis effectors. (National Cancer Institute, Bethesda, MD, USA) Cancer Res. 44:1579-1584, 1984.
Sensenbrenner; Jaros; Moonen, Mandel, Effects of synthetic tripeptide on the differentiation of dissociated cerebral hemisphere nerve cells in culture. (University of Strausbourg, France) Neurobiology 1975 5(4):207-13.
Lindner, Grosse, Halle and Henklein, Uber die Wirkung eines synthetischen Tripeptids auf in vitro kultiviertes Nervengewebe (The effect of a synthetic tripeptide nervous tissue cultured in vitro), (Karl Marx University, Berlin, Germany) Z Mikrosk Anat Forsch 1979;93(5):820-8.
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Ahmed MR, Basha SH, Gopinath D,Muthusamy J, Jayakumar RJ, Initial upregulation of growth factors and inflammatory mediators during nerve regeneration in the presence of cell adhesive peptide-incorporated collagen tubes, J Peripher Nerv Syst. 2005, 10:17-30.
Graham, Diegelmann and Cohen, An in vitro model of fibroblasia - Simultaneous quantification of fibroblast proliferation, migration, and collagen synthesis. (Medical College of Virginia, Richmond, VA, USA) Proc Soc Exp Bio Med 176, 302-308, 1984.
Maquart, Pickart, Laurent, Gillery, Monboisse and Borel, Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. (Laboratoire de Biochimie, CNRS URA 84, Faculte de Medecine, Reims, France. FEBS Lett 1988, 238(2):343-6.
Oddos, T, Jumeau-Lafond, A ; Johnson & Johnson, Val de Reuil, France, Ries, G, Requirement of Copper and Tripeptide Glycyl-L-Histidyl-L-Lysine Complex Formation for Collagen Synthesis Activity in Normal Human Dermal Fibroblasts. Johnson & Johnson, Dusseldorf, Germany Abstract P72, American Academy of Dermatology Meeting, February 2002.
Wegrowski, Maquart, Borel, Stimulation of sulfated glycosaminoglycans by the tripeptide copper complex glycyl-l-histidyl-l-lysine copper(II). (University de Reims, France) Life Sci. 51, 1049-1056, 1992.
Simeon, Wegrowski, Bontemps and Maquart, Expression of glycosaminoglycans and small proteoglycans in wounds: Modulation by the tripeptide copper complex glycyl-histidyl-lysine Cu(II). J Invest Dermatol 2000 Dec;115(6):962-968.
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Maquart, Bellon, Chaqour, Wegrowski, Monboisse, Chastang, Birembaut and Gillery, In vivo stimulation of connective tissue accumulation by the tripeptide- copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. (Universite de Reims, France) J Clin Invest 92: 2368-76, 1993.
Simeon; Monier; Emonard; Gillery; Birembaut, Hornebeck and Maquart, Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine- Cu2+, (Faculte de Medecine, Reims, France) J Invest Dermatol 1999 112(6):957-64.
Simeon, Emonard, Hornebeck & Maquart, The tripeptide-copper complex GHK-Cu stimulates matrix metalloproteinases 2 expression by fibroblast cultures. Laboratoire de Biochimie-UPRESA CNRS 6021, Faculte de Medecine, Reims, France. Life Sci 2000 Sep 22;67(18):2257-65
Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak A.M, Swaim SF, Vangilder J, Lee-Ambrose L, Martin FG, The effect of topical tripeptide-copper complex on healing of ischemic open wounds, Vet Surg. 2003 Nov-Dec;32(6):515-23
Garcia-Sainz JA, Olivares-Reyes JA. Glycyl-histidyl-lysine interacts with the angiotensin II AT1 receptor.Departamento de Bioenergetica, Universidad Nacional Autonoma de Mexico, Mexico D. F. Peptides 1995;16(7):1203-7.
Maquart FX; Simeon A; Pasco S; Monboisse JC. Regulation de l'activite cellulaire par la matrice extracelulaire: le concept de matrikines. J Soc Biol 1999;193(4-5):423-8.
McCormack, M., Nowak KC, Koch, The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model. J. Arch Facial Plast Surg 2001; 3: 28-32.
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Pilgeram LO, Pickart, L Bandi, Z, Fatty acid control of fibrinogen turnover in aging and atherosclerosis. 7th International Congress of Gerontology, June 1964, pp. 451-460. Pickart L, Pilgeram LO. The role of thrombin in fibrinogen biosynthesis. Thromb Diath Haemorrh. 1967 May 31;17(3-4):358-64. Pilgeram LO, Pickart L. Control of fibrinogen biosynthesis: the role of free fatty acid. J Atheroscler Res. 1968, 8:155-66.
Pickart L, Thaler MM. Suppression of tumor-associated hyperfibrinogenemia and free fatty acidemia with p-phenoxybenzalbutyrate (clofibrate). Cancer Res. 1979 Oct;39(10):3845-8.
Pickart, L. Fat metabolism, the fibrinogen/fibrinolytic system and blood flow: new potentials for the pharmacological treatment of coronary heart disease. Pharmacology 1981;23(5):271-80.
Pickart L Suppression of acute-phase synthesis of fibrinogen by a hypolipidemic drug (clofibrate). Int J Tissue React. 1981 3(2):65-72.
Pickart L, Thaler MM. Fatty acids, fibrinogen and blood flow: a general mechanism for hyperfibrinogenemia and its pathologic consequences. Med Hypotheses. 1980 May;6(5):545-57. Pickart L, Thaler MM. Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis. Am J Physiol. 1976 Apr;230(4):996-1002.
Pickart Ph.D. A tripeptide in human plasma that increases the survival of hepatocytes and the growth of hepatoma cells. Thesis in Biochemistry, University of California, San Francisco, 1973.
Thaler MM, Pickart L Metabolic and growth promoting properties of serum tripeptide and its synthetic analog. In: Gene Expression and Carcinogenesis in Cultured Liver. (Academic Press, 1975) pp. 292-310.
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Schlesinger DH, Pickart L, Thaler MM. Related Articles, Protein Growth-modulating serum tripeptide is glycyl-histidyl-lysine. Experientia. 1977 Mar 15;33(3):324-5.
Pickart L, Lovejoy S. Biological activity of human plasma copper-binding growth factor glycyl-L-histidyl-L-lysine. Methods Enzymol. 1987;147:314-28.
Zhai, Chang, Singh, and Maibach, "In vivo nickel contact dermatitis: human model for topical therapeutics", Contact Dermatitis Vol. 40, pp. 205-208, 1999.
Pickart, US Patent 5,118,665 New anti oxidative and anti-inflammatory metal peptide complexes - containing glycine, histidine and lysine residues used to enhance or restore resistance to oxidative or inflammatory damage.
Miller, DeSilva, Pickart, Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. Aust. Pickart and Aust (Biotechnology Center, Utah State University, Logan, UT, USA) Adv. Exp Med Biol 1990;264:79-84.
Coterie N; Tremolieres E; Berliner JCL; Cattier JP; Henichart JP, Redox chemistry of complexes of nickel) with some biologically important peptides in the presence of reduced oxygen species. (INSERM, Ill, France) J Internat BioPharm 1992 Apr;46(1):7-15.
Vinci, Caltabiano, Santoro, Rabuazzo, Buscema, Purrello, Rizzarelli, Vigneri and Purrello, Copper addition prevents the inhibitory effects of interleukin 1-beta on rat pancreatic islets, (University of Catania Medical Endocrinology, University of Catania Medical School, Italy) Diabetologia 1995 38(1):39-45.
Multhaup; Schlicksupp Hesse; Beher; Ruppert Masters; The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I). Beyreuther ( ZMBH-Center for Molecular Biology University of Heidelberg, Germany) Science 1996 Mar 8;271(5254):1406-9.
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Arul V, Gopinath D, Gomathi K, Jayakumar R. Biotinylated GHK peptide incorporated collagenous matrix: A novel biomaterial for dermal wound healing in rats. Biomed Mater Res B Appl Biomater. 2005 May;73(2):383-91.
The influence of medium components on Cu(2+) dependent oxidation of low- density lipoproteins and its sensitivity to superoxide dismutase. Thomas (Marion Merle Dow Research Institute, Cincinnati, Ohio, USA) Biochem Biophys Acta 1992 1128(1):50-7.
Glycyl-histidyl-lysine interacts with the angiotensin II AT1 receptor. Garcia-Sainz JA; Olivares-Reyes JA (Departamento de Bioenergetica, Universidad Nacional Autonoma de Mexico, Mexico D. F). Peptides 1995;16(7):1203-7.
Unpublished studies. Savage, Pickart, et al, Hope Heart Institute, Seattle, Washington, USA.
Unpublished studies. Savage, Pickart, et al, Hope Heart Institute, Seattle, Washington, USA.
An open study of PC1020 (GHK-Cu) rectal solution in treatment of distal inflammatory bowel disease. Levine, Patt, Koren (University of Washington) World Congress of Dermatology, October 1994, Further details presented at 25th Annual Meeting of DDW, Levien, Patt, Koren,Joslin (University of Washington) May 1995.
Pickart US Patent 4,767,753 Copper complexes of histidyl-lysine polypeptide(s) for reducing stomach secretions, increasing stomach mucous and preventing ulcers.
US Patent 5,023,237 Use of polypeptide or its copper complex for cytoprotection in treatment of intestinal and stomach ulcers, and to facilitate wound healing.
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US Patent 5,145,838 Methods and compositions for healing ulcers and peptide derivatives.
Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver, Pickart L, Thaler M, Nature New Biol,1973, 243:85-7.
Smakhtin, MY, Sever’yanova LA, Konoplya AI, Shveinov IA. Tripeptide Gly-His-Lys is a hepatotropic and immunosuppressor. Bull. Exp. Biol. Med. 2002 Jun; 133(6):586-8.
Smakhtin MI, Konoplia AI, Sever’ianova LA, Sheveinov IA. Pharmacological correction of immuno-metabolic disorders with the peptide Gly-His-Lys in hepatic damage induced by tetrachloromethane. Patol Fiziol Eksp Ter. 2003 Apr-Jun; (2):19-21.
Pickart L, US Patent 5,059,588 New and known copper peptide complexes for bone healing containing glycyl-histidyl-lysine and lysyl-histidyl-glycine.
Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype. Godet and Marie (INSERM, Cell and Molecular Biology of Bone and Cartilage, Lariboisiere Hospital, Paris, France) Cell Mol Biol (Noisy-le-grand) 1995 41(8):1081-91.
Effect of the tripeptide glycyl-L-histidyl-L-lysine on the proliferation and synthetic activity of chick embryo chondrocytes. Pesakova, Novotna, and Adam (Institute of Rheumatology, Postgraduate Medical School, Czech Republic) Biomaterials 1995 16(12):911-5.
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Morphological features of bone healing under the effect of collagen-graft-glycosaminoglycan copolymer supplemented with the tripeptide Gly-His-Lys. Pohunkova, Stehlik, Vachal, Cech and Adam Institute of Rheumatology, Charles University, Prague, Czech Republic. Biomaterials 1996, 17(16):1567-74.
Endo, Miyagi, and Ujie, Kissei Pharmaceutical Co., Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L-histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with post-column derivatization.J Chromatogr B Biomed Sci Appl 1997 Apr 25;692(1):37-42.
H-Gly-His psi (NHCO)Lys-OH, partially modified retro-inverso analogue of the growth factor glycyl-L-histidyl-L-lysine with enhanced enzymatic stability. Dalpozzo A, Kanai K, Kereszturi G, Calabrese G. Int J Pept Protein Res 1993 Jun;41(6):561-6.
Copper complexes of glycyl-histidyl-lysine and two of its synthetic analogs: chemical behavior and biological activity, Conato et al, Biochim Biophys Acta 1526, 199-210, 2001.
Pickart US Patent 5,382,431 Tissue protective and regenerative compositions US Patent 5,554,375 Tissue protective and regenerative compositions US Patent 5,698,184 Compositions and methods for skin tanning and protection US Patent 5,888,522 Tissue protective and regenerative compositions.
Methods of controlling proliferation and differentiation of stem and progenitor cells, United States Patent: 6,962,698, Peled, Tony, Fibach, Eitan, Treves; Avi, Gamida Cell Ltd. (Jerusalem, IL) and Hadasit Medical Research Services and Development, Ltd. (Jerusalem, IL)
A tripeptide in human plasma that increases the survival of hepatocytes and the growth of hepatoma cells,. Pickart Ph.D. Thesis in Biochemistry, University of California, San Francisco, 1973
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Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Pickart and Thaler (University of California, San Francisco, USA) Nature New Biol 1973 May 16;243(124):85-7
Growth modulating serum tripeptide is glycyl-histidyl-lysine. Schlesinger, Pickart and Thaler (Harvard University) Experientia 1977, 33(3):324-5.
Effect of transition metals on recovery from plasma of the growth- modulating tripeptide glycylhistidyllysine. Pickart, Thaler and Millard (University of California, San Francisco, USA, US Dept. Agriculture Lab, Albany, CA, USA) J Chromatogr 1979 11;175(1):65-73.
Growth modulating human plasma tripeptide: Relationship between molecular structure and DNA synthesis in hepatoma cells. Pickart and Thaler FEBS Lett 1979, 104(1):119-22
Growth modulating plasma tripeptide may function by facilitating copper uptake into cells. Pickart, Freedman, Loker, Peisach, Perkins, Stenkamp and Weinstein Nature 1980, 288, 715-7.
The use of glycylhistidyllysine in culture systems. Pickart In Vitro 1981,17(6):459-66.
The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth- modulating tripeptide from plasma. Lau and Sarkar Biochem J 1981 199(3):649-56.
Peptide and protein complexes of transition metals as modulators of cell growth. Pickart Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins (Marcel Dekker Pub.) 1982, 75-104.
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NMR. and EPR. investigation of the interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma. Laussac JP; Haran R; Sarkar B Biochem J 1983 Feb 1;209(2):533-9.
PMR studies of Cu(II) and Zn(II) interaction with glycyl-l-histidyl-l-lysine and related peptides. Kwa E, Bor-Sheng L, Rose N, Weinstein B, Pickart L. Peptides 1983, 8, 805-808.
Structure of the glycyl-L-histidyl-L-lysine copper(II) complex in solution. Freedman, Pickart, Weinstein, Mims and Peisach (Albert Einstein Medical School, New York, USA) Biochemistry 1982 21(19):4540-4.
The structure of a copper complex of the growth factor glycyl-l-histidyl-l-lysine at 1.1 angstrom resolution. Perkins CM, Rose NJ, Weinstein B, Stenkamp RE, Jensen, LH, Pickart L. Inorg. Chem Acta 1984, 82, 93-99.
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Cytotoxic chelators and chelates inhibition of DNA synthesis in cultured rodent and human cells by aroylhydrazone analogs of the gly-l-his-l-lys copper(II) complex. Johnson, Pickart and Rose Inorg Chem Acta 67, pp. 159-165, 1982.
Inhibition of the growth of cultured cells and an implanted fibrosarcoma by aroylhydrazone analogs of the Gly-His-Lys-Cu(II) complex. Pickart, Goodwin, Burgua, Murphy and Johnson Biochem Pharmacol 1983, 32(24):3868-71.
The biological effects and mechanism of action of the plasma tripeptide glycyl-l-histidyl-l-lysine. Pickart Lymphokines 8, pp. 425-446, 1983.
Formation of adducts between cupric complexes of known antitumor agents and ehrlich ascites cells. Antholine, Lyman, Petering and Pickart (University of Wisconsin Milwaukee, USA) Biological and Inorganic Copper Chemistry, Adenine Press, pp. 125-137, 1985.
NMR studies on binary and ternary Pd(II) complexes formed by the growth modulating tripeptide glycylhistidyllysine and nucleotides. Laussac, Pasdeloup and Hadjiliadis J Inorg Biochem 30:227-38, 1987.
Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L-histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with post-column derivatization. Endo, Miyagi and Ujiie (Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd., Minamiazumi, Nagano, Japan) J Chromatogr B Biomed Sci Appl 1997, 692(1):37-42.
Brain tissue accumulates 67copper by two ligand dependent saturable processes. A high affinity, low capacity and a low affinity, high capacity process. Hartter and Barnea (Department of Obstetrics and Gynecology, University of Texas Health Science Center, Dallas, USA) J Biol Chem 1988 Jan 15;263(2):799-805.
US Patent 5,120,831 New metal peptide complexes and derivatives used for stimulating growth of hair in warm-blooded animals, especially humans. Pickart US Patent 5,177,061 Compositions for stimulating hair growth containing cupric complexes of peptide derivatives including. glycyl-l-histidyl-l-lysine n-octyl ester. Pickart US Patent 5,214,032 New glycyl-histidyl-lysyl copper compounds used in stimulating hair growth. Pickart US 5,550,183 Metal-peptide compositions and methods for stimulating hair growth. Pickart.
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The hair follicle stimulating properties of peptide copper complexes. Results in C3H mice. Fors, Pickart and Uno Ann N Y Acad Sci 1991 26;642:468-9
Chemical agents and peptides affect hair growth. Uno and Kurata (University of Wisconsin, Madison, USA) J Invest Dermatol 1993 101(1 Suppl):143S-147S
Hairloss protection by peptide-copper complex in animal models of chemotherapy-induced alopecia. Awa and Nogimori Journal Of Dermatological Science, Vol: 10, 1995, 99-104.
Phototrichogram Analysis of Hair Follicle Stimulation: A pilot clinical study with a peptide-copper complex. Patt, Duncan and Kalis (University of Reims, France) Dermatological Research Techniques, (CRC Press), pp-217-226, 1996.
Quantitative Assessment of Peptide-Copper Complex Induced Hair Follicle Stimulation Using the Fuzzy Rat, Uno, Packard, Patt (University of Wisconsin) Dermatological Research Techniques, (CRC Press), pp-227-239, 1996.
Evaluation of Telogen Hair Follicle Stimulation Using an In Vivo Model: Results with Peptide Copper Complexes. Timpe, Dumwiddie, Patt (Procyte Corp.) Dermatological Research Techniques, (CRC Press), pp-241-254, 1996.
Procyte Corp. press release 1997
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Pickart US Patent 5,554,375 Tissue protective and regenerative compositions.
Pickart L, Effect of copper peptides on hair growth and condition, Body Language Dermatology 2004, Number 7, pages 20-22.
Pickart L, Skin remodeling copper peptides for improving hair growth, Cosmetics & Medicine (Russia) 2004, Number 3, pages 14-29.
Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L-histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with post-column derivatization, Endo T; Miyagi M; Ujiie A (Kissei Pharmaceutical Co., Ltd., Minamiazumi, Nagano, Japan) J Chromatogr B Biomed Sci Appl 1997 Apr 25;692(1):37-42.
Maquart et al 1999, Simeon et al 1999, Simeon et al 2000.
Zhai, Leow, and Maibach, "Sodium lauryl sulfate damaged skin in vivo in man: a water barrier repair model", Skin Research and Technology, Volume 4, pages 24-27, 1998. Skin Biology's product markedly accelerated the repair of skin damaged by the application of an irritating detergent.
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Zhai, Poblete, and Maibach, "Stripped skin model to predict irritation potential of topical agents in vivo in man", International Journal of Dermatology, Volume 37, pages 386-389, 1998; Skin Biology product increased skin repair after skin removal by repeated tape-stripping.
Zhai, Leow, and Maibach, "Human barrier recovery after acute acetone perturbation: an irritant dermatitis model", Clinical and Experimental Dermatology, Volume 23, pages 11-13, 1998. Skin was damaged by a fat removing agent, acetone, then treated with a Skin Biology product which rapidly rebuilt the damaged skin.
Zhai, Chang, Singh, and Maibach, "An in vivo nickel allergy contact dermatitis human model for topical therapeutics", Presented in February 1998, American Academy of Dermatology Meeting. Skin was damaged by the application of nickel salts to persons with nickel allergy. The Skin Biology product increased skin repair and reduced skin irritation.
Zhai, Leow, and Maibach, "Human barrier recovery after acute acetone perturbation: An Irritant Dermatitis Model", Clinical and Experimental Dermatology, Volume 23, pages 11-13, 1998.
Stern, Robert S. and Laid, Nan. "The carcinogenic risk of treatments for severe psoriasis". Cancer, Vol. 73, No. 11, June 1, 1994, pp. 2759-64.
Hawaii Dermatology Seminar, 1997.
Skin and Allergy News, April 1997, Hawaii Dermatology Seminar, 1997.
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Cosmetic Industry
The Cosmetic Counter, March 1999.
Zhai, Chang, Singh, and Maibach, "In vivo nickel contact dermatitis: human model for topical therapeutics", Contact Dermatitis Vol. 40, pp. 205-208, 1999.
Lee, A. and Langer, R.: (Shark Liver Extract Contains Inhibitors of Tumor Angiogenesis) Science 221:1185-86, 1983
"Identification of Polar Volatile Organic Compounds in Consumer Products and Common Microenvironments," 1991 Reference: Lance Wallace, EPA.
Skin and Allergy News, April 1997.
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Lopez A; Sims DE; Ablett RF; Skinner RE; Leger LW; Lariviere CM; Jamieson LA; Martinez-Burnes J; Zawadzka GG Effect of emu oil on auricular inflammation induced with croton oil in mice. Am J Vet Res 1999 Dec;60(12):1558-61.
Politis MJ; Dmytrowich A, Promotion of second intention wound healing by Emu Oil lotion: comparative results with furasin, polysporin, and cortisone. Plast Reconstr Surg 1998 Dec;102(7):2404-7.
Zemtsov A; Gaddis M; Montalvo-Lugo VM, Moisturizing and cosmetic properties of Emu Oil: a pilot double blind study, Australas J Dermatol 1996 Aug;37(3):159-61.
Masuda, A. et al, Potentiation of Anti-fungal Effect of Amphotericin B by Squalene, An Intermediate For Sterol Biosynthesis. J. Antibiot. 35(2): 230-234, 1982.
Storm, HM, Oh SY, Kimler BF, Norton S., R