Age-related alterations in the signal transduction pathways of the elastin-laminin receptor.
With aging we assist to alterations in the vascular structure and function. One important factor in these vascular wall changes is the degradation of the elastin fibre major protein: elastin. Elastin peptides derived from the degradation are present in human sera. Elastin peptides induce on fibroblasts, phagocytic cells, lymphocytes, smooth muscle cells and endothelial cells, a variety of biological effects mediated by the elastin-laminin receptor which has been demonstrated to be present on the membrane of these cells. The transduction pathway of the ELR receptor involves the activation of phospholipase C (PLC) by a pertussis toxin sensitive G-protein. PLC induces the production of inositol trisphosphate (IP3) leading to the increase of the intracellular free calcium on one hand, and of diacylglycerol (DAG) which stimulates the translocation to the membrane of PKC leading to the phosphorylation of members of the MAPK family, such as p42/p44 MAPK. A progressive age dependent uncoupling of the elastin-laminin receptor occurs impairing its transduction pathway and which results in alteration of the calcium signaling and loss in calcium homeostasis of the cells. These alterations in the signal transduction of the elastin-laminin receptor result in modified activities of parenchymal and phagocytic cells with aging, such as free radical production and elastase release. Thus, these age-related alterations in the elastin-laminin receptor signal transduction may be involved in the atherogenesis.
Fulöp
T
T
Laboratoire de biogérontologie, institut universitaire de gériatrie et département de médecine interne, faculté de médecine, université de Sherbrooke, Québec, Canada. tfulop@courrier.usherb.ca
Douziech
N
N
Jacob
M P
MP
Hauck
M
M
Wallach
J
J
Robert
L
L
D000375:Aging; D001161:Arteriosclerosis / Q000209:etiology; D001808:Blood Vessels / Q000378:metabolism; D004549:Elastin / Q000097:blood; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D037342:Pertussis Toxin; D010586:Phagocytes / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D017474:Receptors, Laminin / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011956:Receptors, Cell Surface; D017474:Receptors, Laminin; D010566:Virulence Factors, Bordetella; C054901:elastin-binding proteins; D004549:Elastin; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins