HDAC inhibitor trichostatin A-inhibited survival of dopaminergic neuronal cells.
Histone deacetylase (HDAC) inhibitors have been shown associated with neurodegenerative diseases. However, their effects on survival of dopaminergic neurons remain uncertain. In the present study, the HDAC inhibitor trichostatin A (TSA) was tested in following dopaminergic neuronal cell lines: rat N27, mouse MN9D, and human SH-SY5Y cells. Results demonstrated that a single TSA treatment resulted in decreased cell survival and increased apoptosis in dopaminergic neuronal cells. Pre-treatment with TSA resulted in exacerbated neurotoxic damage to dopaminergic neurons induced by 1-methyl-4-phenylpyridinium and rotenone. These results suggest that HDAC inhibitors may influence Parkinson's disease pathogenesis by inhibiting survival and increasing vulnerability of dopaminergic neurons to neurotoxins. Our data also suggested the importance of prudent use of HDAC inhibitors in therapy.
Wang
Yong
Y
Department of Physiology and Key Laboratory of the Neurodegenerative Disorders of the Chinese Ministry of Education, Capital Medical University, Youanmen, Beijing 100069, China.
Wang
Xuan
X
Liu
Limin
L
Wang
Xiaomin
X
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D020022:Genetic Predisposition to Disease; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D012402:Rotenone / Q000633:toxicity; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology
D000978:Antiparkinson Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012402:Rotenone; C012589:trichostatin A; D006655:Histone Deacetylases; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine