Pickart, Loren
(Skin Biology, Research & Development Department, 4122 Factoria Boulevard SE, Suite No. 200, Bellevue, WA 98006, USA)
,
Vasquez-Soltero, Jessica
(Skin Biology, Research & Development Department, 4122 Factoria Boulevard SE, Suite No. 200, Bellevue, WA 98006, USA)
,
Margolina, Anna
(Skin Biology, Research & Development Department, 4122 Factoria Boulevard SE, Suite No. 200, Bellevue, WA 98006, USA)
The copper binding tripeptide GHK (glycyl-l-histidyl-l-lysine) is a naturally occurring plasma peptide that significantly declines during human aging. It has been established that GHK:Copper(2+) improves wound healing and tissue regeneration and stimulates collagen and decorin production. GHK-Cu als...
The copper binding tripeptide GHK (glycyl-l-histidyl-l-lysine) is a naturally occurring plasma peptide that significantly declines during human aging. It has been established that GHK:Copper(2+) improves wound healing and tissue regeneration and stimulates collagen and decorin production. GHK-Cu also supports angiogenesis and nerve outgrowth, improves the condition of aging skin and hair, and possesses antioxidant and anti-inflammatory effects. In addition, it increases cellular stemness and secretion of trophic factors by mesenchymal stem cells. GHK’s antioxidant actions have been demonstrated in vitro and in animal studies. They include blocking the formation of reactive oxygen and carbonyl species, detoxifying toxic products of lipid peroxidation such as acrolein, protecting keratinocytes from lethal Ultraviolet B (UVB) radiation, and blocking hepatic damage by dichloromethane radicals. In recent studies, GHK has been found to switch gene expression from a diseased state to a healthier state for certain cancers and for chronic obstructive pulmonary disease (COPD). The Broad Institute’s Connectivity Map indicated that GHK induces a 50% or greater change of expression in 31.2% of human genes. This paper reviews biological data demonstrating positive effects of GHK in skin and proposes interaction with antioxidant-related genes as a possible explanation of its antioxidant activity.
The copper binding tripeptide GHK (glycyl-l-histidyl-l-lysine) is a naturally occurring plasma peptide that significantly declines during human aging. It has been established that GHK:Copper(2+) improves wound healing and tissue regeneration and stimulates collagen and decorin production. GHK-Cu also supports angiogenesis and nerve outgrowth, improves the condition of aging skin and hair, and possesses antioxidant and anti-inflammatory effects. In addition, it increases cellular stemness and secretion of trophic factors by mesenchymal stem cells. GHK’s antioxidant actions have been demonstrated in vitro and in animal studies. They include blocking the formation of reactive oxygen and carbonyl species, detoxifying toxic products of lipid peroxidation such as acrolein, protecting keratinocytes from lethal Ultraviolet B (UVB) radiation, and blocking hepatic damage by dichloromethane radicals. In recent studies, GHK has been found to switch gene expression from a diseased state to a healthier state for certain cancers and for chronic obstructive pulmonary disease (COPD). The Broad Institute’s Connectivity Map indicated that GHK induces a 50% or greater change of expression in 31.2% of human genes. This paper reviews biological data demonstrating positive effects of GHK in skin and proposes interaction with antioxidant-related genes as a possible explanation of its antioxidant activity.
참고문헌 (64)
Young Antioxidants in health and disease J. Clin. Pathol. 2001 10.1136/jcp.54.3.176 54 176
10.1155/2014/860479 Godic, A., Poljsak, B., Adamic, M., and Dahmane, R. (2014). The role of antioxidants in skin cancer prevention and treatment. Oxid. Med. Cell. Longev., 2014.
Wang Dual effects of antioxidants in neurodegeneration: Direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation Curr. Pharm. Des. 2006 10.2174/138161206778343109 12 3521
Pickart The human tri-peptide GHK and tissue remodeling J. Biomater. Sci. Polym. Ed. 2008 10.1163/156856208784909435 19 969
Pickart A possible mechanism whereby skin remodeling may suppress cancer metastasis genes Wound Repair and Regeneration 2011 Volume 19 A62
Pickart, L. (1973). A Tripeptide in Human Plasma that Increases the Survival of Hepatocytes and the Growth of Hepatoma Cells. [Ph.D. Thesis, University of California].
Pickart Growth-modulating tripeptide (glycylhistidyllysine): Association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes J. Cell. Physiol. 1980 10.1002/jcp.1041020205 102 129
Schlesinger Growth-modulating serum tripeptide is glycyl-histidyl-lysine Cell. Mol. Life Sci. 1977 10.1007/BF02002806 33 324
Lane SPARC is a source of copper-binding peptides that stimulate angiogenesis J. Cell. Biol. 1994 10.1083/jcb.125.4.929 125 929
Pickart Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells Nature 1980 10.1038/288715a0 288 715
Lau The interaction of copper(II) and glycyl-l-histidyl-l-lysine, a growth-modulating tripeptide from plasma Biochem. J. 1981 10.1042/bj1990649 199 649
Pickart The use of glycylhistidyllysine in culture systems In Vitro 1981 10.1007/BF02633506 17 459
Williams Glycyl-l-histidyl-l-lysine, a growth promoting factor for human cells Cytobios 1979 27 19
Barra Effects of glycyl-histidyl-lysine on Morris hepatoma 7777 cells Cytobios 1986 52 99
Pollard Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts Arch. Facial Plast. Surg. 2005 10.1001/archfaci.7.1.27 7 27
Lamb The connectivity map: A new tool for biomedical research Nat. Rev. Cancer 2007 10.1038/nrc2044 7 54
Iorio Discovery of drug mode of action and drug repositioning from transcriptional responses Proc. Natl. Acad. Sci. 2010 10.1073/pnas.1000138107 107 14621
Hong A “metastasis-prone” signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics Clin. Exp. Metastasis 2010 10.1007/s10585-010-9305-4 27 83
Campbell A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK Genome Med. 2012 4 1
10.1155/2014/151479 Pickart, L., Vasquez-Soltero, J.M., and Margolina, A. (2014). GHK and DNA: Resetting the human genome to health. Biomed. Res. Int., 2014.
Pickart, L. (1988). Use of GHL-Cu as a Wound-Healing and Anti-Inflammatory Agent. (No. 4,760,051), U.S. Patent.
Downey Acceleration of wound healing using glycyl-histidyl-lysine copper (II) Surg. Forum 1985 25 573
Maquart Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu2+ FEBS Lett. 1988 10.1016/0014-5793(88)80509-X 238 343
Maquart In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu2+ in rat experimental wounds J. Clin. Invest. 1993 10.1172/JCI116842 92 2368
Wegrowski Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu2+ Life Sci. 1992 10.1016/0024-3205(92)90504-I 51 1049
Simeon The tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures Life Sci. 2000 10.1016/S0024-3205(00)00803-1 67 2257
Simeon Expression of glycosaminoglycans and small proteoglycans in wounds: Modulation by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu(2+) J. Invest. Dermatol. 2000 10.1046/j.1523-1747.2000.00166.x 115 962
Gul The effects of topical tripeptide copper complex and helium-neon laser on wound healing in rabbits Vet. Dermatol. 2008 10.1111/j.1365-3164.2007.00647.x 19 7
Cangul Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits Vet. Dermatol. 2006 10.1111/j.1365-3164.2006.00551.x 17 417
Pickart, L. (1992). Method of Using Copper(II) Containing Compounds to Accelerate Wound Healing. (No. 5,164,367), U.S. Patent.
Arul A therapeutic approach for diabetic wound healing using biotinylated GHK incorporated collagen matrices Life Sci. 2007 10.1016/j.lfs.2006.09.018 80 275
Canapp The effect of topical tripeptide-copper complex on healing of ischemic open wounds Vet. Surg. 2003 10.1111/j.1532-950X.2003.00515.x 32 515
Swaim Effect of locally injected medications on healing of pad wounds in dogs Am. J. Vet. Res. 1996 10.2460/ajvr.1996.57.03.394 57 394
Thomas The influence of medium components on Cu2+-dependent oxidation of low-density lipoproteins and its sensitivity to superoxide dismutase Biochim. Biophys. Acta 1992 10.1016/0005-2760(92)90256-U 1128 50
Beretta Acrolein sequestering ability of the endogenous tripeptide glycyl-histidyl-lysine (GHK): Characterization of conjugation products by ESI-MSn and theoretical calculations J. Pharm Biomed. Anal. 2008 10.1016/j.jpba.2008.02.012 47 596
Beretta Glycyl-histidyl-lysine (GHK) is a quencher of α,β-4-hydroxy-trans-2-nonenal: A comparison with carnosine. Insights into the mechanism of reaction by electrospray ionization mass spectrometry, 1H NMR, and computational techniques Chem. Res. Toxicol. 2007 10.1021/tx700185s 20 1309
Smakhtin [Pharmacological correction of immuno-metabolic disorders with the peptide Gly-His-Lys in hepatic damage induced by tetrachloromethane] Patol. Fiziol. Eksp. Ter. Russ. 2003 2 19
Cherdakov Synergetic antioxidant and reparative action of thymogen, dalargin and peptide Gly-His-Lys in tubular bone fractures Exp. Biol. Med. 2010 4 15
Miller Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation Adv. Exp. Med. Biol. 1990 10.1007/978-1-4684-5730-8_11 264 79
Pickart, L. (1992). Anti-Oxidative and Anti-Inflammatory Metal:Peptide Complexes and Uses Thereof. (No. 07/478,091), U.S. Patent.
Pickart GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes J. Anal. Oncol. 2014 3 79
Mariappan NF-kappaB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes Cardiovasc. Res. 2010 10.1093/cvr/cvp305 85 473
Vermeij Proteomic identification of in vivo interactors reveals novel function of skin cornification proteins J. Proteome Res. 2012 10.1021/pr300310b 11 3068
Liu Wound repair and anti-oxidative capacity is regulated by ITGB4 in airway epithelial cells Mol. Cell. Biochem. 2010 10.1007/s11010-010-0457-y 341 259
Elsoe Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL Atherosclerosis 2012 10.1016/j.atherosclerosis.2011.11.031 221 91
Kempster Disruption of paraoxonase 3 impairs proliferation and antioxidant defenses in human A549 cells and causes embryonic lethality in mice Am. J. Physiol. Endocrinol. Metab. 2012 10.1152/ajpendo.00357.2011 302 E103
Song Ferroportin1 and hephaestin overexpression attenuate iron-induced oxidative stress in MES23.5 dopaminergic cells J. Cell. Biochem. 2010 10.1002/jcb.22617 110 1063
Rosenblat Paraoxonase 1 (PON1) is a more potent antioxidant and stimulant of macrophage cholesterol efflux, when present in HDL than in lipoprotein-deficient serum: Relevance to diabetes Atherosclerosis 2006 10.1016/j.atherosclerosis.2005.08.026 187 74
Hussain Role of metallothionein and other antioxidants in scavenging superoxide radicals and their possible role in neuroprotection Neurochem. Int. 1996 10.1016/0197-0186(95)00114-X 29 145
Itahana The uric acid transporter SLC2A9 is a direct target gene of the tumor suppressor p53 contributing to antioxidant defense Oncogene 2015 10.1038/onc.2014.119 34 1799
Chen Induction of cytoprotective genes through Nrf2/antioxidant response element pathway: A new therapeutic approach for the treatment of inflammatory diseases Curr. Pharm. Des. 2004 10.2174/1381612043452901 10 879
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