Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycl-L-histidyl-L-lysine-Cu
ABSTRACT Glycyl-L-histidyl-L-lysine (GHK) is a tripeptide with affinity for copper(II) ions and was isolated from human plasma. This peptide appears to play a physiological role in wound healing. We report the stimulating effect of GHK-Cu on collagen synthesis by fibroblasts. The stimulation began between 10−12 and 10−11 M, maximized at 10−9 M, and was independent of any change in cell number. The presence of a GHK triplet in the α2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing effects.
Full-textDOI: · Available from: Loren Pickart, Jul 30, 2015
- SourceAvailable from: Thomas P Vacek
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- "The following are characteristic of ECM remodelling that can contribute to stiffness and systolic/diastolic failure: total collagen content, collagen subtypes, collagen protein stability, collagen cross-linking (Iimoto et al., 1988; Jalil et al., 1989; Mukherjee & Sen 1990; Norton et al., 1997). The activation of MMPs involves collagen degradation with replacement of fibrotic tissue (Dollery et al., 1995; Li et al., 2000b; Maquart et al., 1988). "
ABSTRACT: High levels of homocysteine (Hcy), known as hyperhomocysteinmia (HHcy), are correlated with an increase in extracellular matrix remodelling (ECM) via the matrix metalloproteinases (MMPs) and plasminogen/plasmin system. This results in an increase deposition of collagen that leads to endothelial-myocyte (EM) and myocyte-myocyte (MM) uncoupling; the physiological consequences are a plethora of cardiovascular pathologies. Homocysteine-induced increase in intracellular and mitochondrial Ca(2+) plays an important role in increasing reactive oxygen species (ROS) within mitochondria and instigating mitophagy within the cell. This occurs via several Hcy-mitigated processes: agonizing N-methyl-d-aspartate receptor-1 (NMDA-R1), decreasing expression of peroxisome proliferator activator receptor (PPAR) [thereby increasing oxidation], impairing Ca(2+) handling via Na(+)/Ca(2+) exchanger (NCX1) and Sarco endoplasmic reticulum Ca(2+) ATPase (SERCA-2a). The end result is an increase in ROS that directly or indirectly lead to MMP activation within mitochondria or the cytoplasm. Hcy induces a mitochondrial permeability transition that allows MMPs to be released from mitochondria thereby metabolizing matrix and impairing cardiac function. Further work remains to be elucidated concerning the specific mitochondrial mitophagic mechanisms under which matrix metabolism and remodelling occurs. Moreover, the therapeutic implications of NMDA and PPAR ligands are some promise to patient.Archives of Physiology and Biochemistry 12/2011; 118(1):31-42. DOI:10.3109/13813455.2011.635660
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ABSTRACT: Thesis (Ph. D.)--University of Southern California, 1991. Includes bibliographical references (leaves 93-94).