Expression of Transcriptional Repressor Proteins mSin3A and 3B during Aging and Replicative Senescence

• Published in: Biochemical and biophysical research communications 2000-08, Vol.275 (2), p.455-459
• Main Authors: Kyrylenko, Sergiy, Korhonen, Pauliina, Kyrylenko, Olga, Roschier, Maaria, Salminen, Antero
• Format: Article
• Language: English
• Subjects: Animals; Cell Division; Cell Line, Transformed; Cellular Senescence; chromatin; histone acetylation; histone deacetylase; Humans; Male; methyl-CpG-binding protein; Rats; Repressor Proteins - genetics; RNA, Messenger - genetics; Simian virus 40; Sin3A protein; Sin3B protein; Transcription Factors - genetics; Transcription, Genetic; WI-38 fibroblasts
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3325

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.