Age-related attenuation of HSP47 heat response in fibroblasts.
The collagen-binding heat shock protein of molecular weight 47,000 (HSP47), resident in the endoplasmic reticulum (ER), is assumed to play a specific role as a molecular chaperon in the processing of procollagen molecules. The present investigation of age-related alteration in the HSP47 heat response in cultured murine and human fibroblasts revealed expression in cells with a low population doubling level (PDL) derived from young mice and people more inducible by heat treatment than those from older mice and people. On the other hand, cells with a high PDL showed a very low heat response in terms of HSP47 expression regardless of the donor age. Northern blot analysis of HSP47 m-RNA indicated that the age related attenuation of HSP47 expression was regulated by transcriptional mechanisms. Furthermore, immunofluorescent analysis using a monoclonal antibody against the carboxylterminal propeptide of type I procollagen revealed far greater retention of procollagen molecules in the ER lumen of cells from old persons than in those from young persons. This was particularly prominent in heat-treated cells from old persons, indicating the possibility that the observed decrease in HSP47 heat response might cause blockage of procollagen transport to the Golgi and therefore secretion.
Miyaishi
O
O
Institute for Medical Science of Aging, Aichi Medical University, Japan.
Ito
Y
Y
Kozaki
K
K
Sato
T
T
Takechi
H
H
Nagata
K
K
Saga
S
S
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000378:metabolism
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015335:Molecular Probes; D011347:Procollagen; C494660:SERPINH1 protein, human; C494661:Serpinh1 protein, mouse