Age-related alteration of proline hydroxylase and collagen-binding heat shock protein (HSP47) expression in human fibroblasts

Changes in the expression of α and β subunits of proline 4-hydroxylase (PHα and PHβ) and HSP47, implicated as a molecular chaperone specific for procollagen processing, were examined in human embryonal fibroblasts in relation to in vitro aging. For this purpose a model with treatments causing the decreased hydroxylation of proline residues in procollagens was used. In cells at a low population doubling level (PDL) induction of PHα, PHβ, and HSP47 by depletion of ascorbate or addition of α-α′ dipyridyl could be clearly demonstrated by immunoprecipitation and Northern blotting. In contrast, the induction of PHα and HSP47 expression was markedly attenuated in high PDL cells, indicating an age-related decrease in response to procollagen retention in the ER caused by hypohydroxylation of proline residues of procollagens.