Sodium Selenite Induces Apoptosis in Cultured Cortical Neurons with Special Concomitant Changes in the Expression of Apoptosis-related Genes
Sodium selenite was used to examine whether a selenium compound is able to trigger apoptotic degeneration in cultured cortical neurons in vitro, and to explore detailed changes in the expression of related genes during apoptotic processes using molecular biological and flow cytometric investigations. The results indicated that: (1) cortical neurons treated with sodium selenite at different dosages (0.0008, 0.004, 0.0200, 0.1000 and 0.5000 microM) and different exposure times (2, 4, 24, and 48 h) exhibited dose- and time-dependent apoptotic processes as revealed by typical DNA ladder formation detected by agarose gel electrophoresis; (2) internucleosomal DNA fragmentation detected by flow cytometric examination showed a prominent peak of hypodiploid DNA contents as early as 4 h after exposure to 0.1 microM sodium selenite; (3) DNA fragmentation induced by sodium selenite as revealed by the above two methods could be blocked by aurintricarboxylic acid; (4) transcription of mRNAs related to bcl-2, bax, c-fos, p53, and acetylcholinesterase (AChE) genes, as detected by RT-PCR assays, showed down-regulation for bcl-2 and up-regulation for bax, c-fos, p53 and AChE genes after exposure to sodium selenite. This study suggests that sodium selenite is effective in the induction of apoptosis in cultured cortical neurons, and that relevant changes in the expression of several apoptosis-related genes might further our understanding of the mechanism(s) which initiate and maintain apoptotic processes.