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Kinetics of 125 I‐PDGF binding and down‐regulation of PDGF receptor in human arterial smooth muscle cell strains during cellular senescence in vitro
Author(s) -
Aoyagi Masaru,
Fukai Naomi,
Ogami Kazuo,
Yamamoto Mari,
Yamamoto Kiyotaka
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041640218
Subject(s) - platelet derived growth factor receptor , receptor , platelet derived growth factor , biology , microbiology and biotechnology , senescence , tyrosine phosphorylation , growth factor , internalization , endocrinology , medicine , biochemistry
Platelet‐derived growth factor (PDGF) is one of the major mitogens in serum to stimulate replication of human smooth muscle cells (SMCs) in culture. Previous studies using human fibroblasts failed to demonstrate changes in the receptor systems for growth factors during cellular senescence. We investigated the kinetics of 125 I‐PDGF(‐BB) binding and down‐regulation of the PDGF receptor in three human arterial SMC strains during cellular aging. The number of specific 125 I‐PDGF binding sites per cell increased slightly at a population doubling level (PDL) of 60%–80% of life span and then decreased at the PDL above 90%. The number of receptors per cell‐surface area decreased with increasing in vitro age. The apparent Kd for the 125 I‐PDGF binding decreased with in vitro senescence. The internalization and degradation of 125 I‐PDGF per receptor were significantly reduced in senescent SMCs than young cells. Furthermore, down‐regulation of the PDGF receptor was significantly greater in sensescent SMCs than young cells. Immunoblot studies demonstrated that changes in b̃‐subunit of the PDGF receptor accounted for those in the studies using 125 I‐PDGF and that tyrosine phosphorylation of the PDGF receptor was significantly greater in young SMCs than aged cells. Our results suggest that age‐related changes in the receptor systems for PDGF may be important contributors to the failure of DNA synthesis in senescent SMCs. © 1995 Wiley‐Liss, Inc.