AGE-RELATED ATTENUATION OF HSP47 HEAT RESPONSE IN FIBROBLASTS

The collagen-binding heat shock protein of molecular weight 47 000 (HS P47), resident in the endoplasmic reticulum (ER), is assumed to play a specific role as a molecular chaperon in the processing of procollage n molecules. The present investigation of age-related alteration in th e HSP47 heat response in cultured murine and human fibroblasts reveale d expression in cells with a low population doubling level (PDL) deriv ed from young mice and people more inducible by heat treatment than th ose from older mice and people. On the other hand, cells with a high P DL showed a very low heat response in terms of HSP47 expression regard less 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 u sing a monoclonal antibody against the carboxylterminal propeptide of type I procollagen revealed far greater retention of procollagen molec ules in the ER lumen of cells from old persons than in those from youn g 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 t he Golgi and therefore secretion.