Expression of transcriptional repressor protein mSin3A but not mSin3B is induced during neuronal apoptosis

mSin3 proteins have an important role in transcriptional repression mediated by histone deacetylation. Our purpose was to find out whether apoptosis affects the expression of mSin3 proteins in neuroblastoma 2a cells. We observed that neuronal apoptosis, induced by serum withdrawal or by treatment with etoposide, okadaic acid or trichostatin A, induced a prominent increase in mSin3A protein expression but did not affect the level of mSin3B protein. Trichostatin A, an inhibitor of histone deacetylases, induced the most prominent upregulation of mSin3A protein. Metabolic labeling and immunoprecipitation of mSin3A showed a marked increase in the synthesis of mSin3A protein in agreement with the immunoblotting results. Interestingly, the expression of mSin3A preceded the activation of caspase-3 and the execution phase of neuronal apoptosis. These results suggest that the expression of mSin3A proteins may provide a regulation mechanism to enhance transcriptional repression or silencing of genes during neuronal apoptosis, as well as during degenerative diseases. (C) 1998 Academic Press.