Expression of transcriptional repressor proteins mSin3A and 3B during aging and replicative senescence.
Sin3 proteins have a key role in transcriptional repression mediated by histone deacetylation. Mammalian Sin3 proteins, mSin3A and 3B, act as adapter molecules which bind both to repressive transcription factors and to the methyl-CpG-binding proteins (MeCPs) and recruit histone deacetylases to assemble a multiprotein repressor complex. We have recently observed (Biochem. Biophys. Res. Commun. 252, 274-277, 1998) that the expression of mSin3A but not mSin3B protein is induced during neuronal apoptosis. The purpose of this study was to find out whether aging and replicative senescence affect the expression levels of mSin3A and 3B repressor proteins. We studied the expression levels of mSin3A and 3B mRNAs and proteins both in replicative senescence model of WI-38 fibroblasts and in liver and brain tissues of young (4-6 months) and old (26-30 months) male Wistar rats. Replicative senescence of human WI-38 fibroblasts did not affect the expression levels of mSin3A and 3B mRNAs. However, the late passage WI-38 fibroblasts showed a significant 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 levels of either mSin3A or mSin3B mRNAs in the liver and frontal cortex. Similarly, the protein levels of mSin3A and 3B were unaffected in the hippocampus, cerebellum and liver tissues during aging. These results show that aging in vivo, in contrast to replicative senescence, does not affect the expression levels of mSin3A and 3B repressor proteins. However, this does not exclude the possible age-related functional changes mediated by mSin3-histone deacetylase complexes.
Kyrylenko
S
S
Department of Neuroscience and Neurology, University of Kuopio, Kuopio, FIN-70211, Finland.
Korhonen
P
P
Kyrylenko
O
O
Roschier
M
M
Salminen
A
A
D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D016922:Cellular Senescence; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C492042:SIN3B protein, human; D014157:Transcription Factors; D056264:Sin3 Histone Deacetylase and Corepressor Complex