Sodium selenite induces apoptosis in cultured cortical neurons with special concomitant changes in expression of the apoptosis-related genes.
Sodium selenite was used to examine whether selenium compound is able to trigger apoptotic degeneration in cultured cortical neurons in vitro and to explore the detailed changes in expression of the related genes during the apoptotic processes using molecular biological and flow cytometric examinations. The results indicated that: (1) cortical neurons treated with sodium selenite with 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) the internucleosomal DNA fragmentation detected by flow cytometric examination showed a prominent peak of hypodiploid DNA contents as early as 4h after exposure of 0.1 microM sodium selenite; (3) the DNA fragmentation induced by sodium selenite as revealed by the above two examinations could be blocked by aurintricarboxylic acid; (4) the transcriptions 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 of sodium selenite. This study suggests that the sodium selenite is effective for inducing apoptosis in cultured cortical neurons and that relevant changes in expression of several apoptosis-related genes might further our understanding of the mechanism(s) that initiates and maintains the apoptotic processes.
Department of Nutrition and Food Hygiene, Capital University of Medical Sciences, Beijing 100069, PR China.
R
R
Xiao
Jian T
JT
Qiao
Hai F
HF
Zhao
J
J
Liang
Huan L
HL
Yu
J
J
Liu
Ai M
AM
Guo
W
W
Wang
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018038:Sodium Selenite / Q000494:pharmacology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000110:Acetylcholinesterase; D018038:Sodium Selenite