Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells.
The present studies investigated the effects of tacrine, a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H(2)O(2))-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H(2)O(2) (100 microM) triggered typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed upregulated p53 and bax mRNA levels with H(2)O(2) treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with tacrine significantly attenuated H(2)O(2)-induced injury, prevented the cells from apoptosis and attenuated H(2)O(2)-induced overexpression of bax and p53. The present findings suggest that tacrine exert significant protection against H(2)O(2)-induced apoptosis possibly through inhibiting expression of pro-apoptosis genes.
Wang
Rui
R
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-yuan Road, Shanghai 200031, PR China.
Zhou
Jin
J
Tang
Xi Can
XC
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013619:Tacrine / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D018697:Nootropic Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D013619:Tacrine; D006861:Hydrogen Peroxide