Expression of transcriptional repressor proteins mSin3A and 3B during aging and replicative senescence

Sin3 proteins have a key role in transcriptional repression mediated by his tone deacetylation, Mammalian Sin3 proteins, mSin3A and 3B, act as adapter molecules which bind both to repressive transcription factors and to the me thyl-CpG-binding proteins (MeCPs) and recruit histone deacetylases to assem ble a multiprotein repressor complex. We have recently observed (Biochem. B iophys. Res. Commun. 252, 274-277, 1998) that the expression of mSin3A but not mSin3B protein is induced during neuronal apoptosis, The purpose of thi s study was to find out whether aging and replicative senescence affect the expression levels of mSin3A and 3B repressor proteins. We studied the expr ession levels of mSin3A and 3B mnNAs and proteins both in replicative senes cence model of WI-38 fibroblasts and in liver and brain tissues of young (4 -6 months) and old (26-30 months) male Wister rats. Replicative senescence of human WI-38 fibroblasts did not affect the expression levels of mSin3A a nd 3B mRNAs. However, the late passage WI-38 fibroblasts showed a significa nt decline in the expression level of mSin3A protein. Immortalization of WI -38 fibroblasts with SV-40 transformation increased the expression level of 6.0 kb mSin3A mRNA Aging of Wistar rats did not affect; the expression lev els of either mSin3A or mSin3B mRNAs in the liver and frontal cortex. Simil arly, the protein levels of mSin3A and 3B were unaffected in the hippocampu s, cerebellum and liver tissues during aging These results show that aging in vivo, in contrast to replicative senescence, does not affect the express ion levels of mSin3A and 3B repressor proteins. However, this does not excl ude the possible age-related functional changes mediated by mSin3-histone d eacetylase complexes. (C) 2000 Academic Press.