Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells.
The present studies investigated effects of huperzine A (HupA), a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H2O2)-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H2O2 (100 microM) triggered a typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed up-regulated p53 and Bax but lowered Bcl-2 mRNA levels with H2O2 treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with HupA (1 microM) significantly prevented the cells from apoptosis, attenuated H2O2-induced over-expression of Bax and p53, and rehabilitated the level of Bcl-2. The present findings suggest that HupA exerts significant protection against H2O2-induced apoptosis, possibly through improving expression of apoptosis-related genes.
Wang
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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.
Xiao
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Tang
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D000470:Alkaloids; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000470:Alkaloids; C494828:Bax protein, rat; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D016877:Oxidants; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C050426:huperzine A; D006861:Hydrogen Peroxide