title: Heat shock transcription factor-1 suppresses apoptotic cell death and ROS generation in 3-nitropropionic acid-stimulated striatal cells.
abstract: Striatal neuronal cell death is one of the pathological features of Huntington's disease (HD). Overexpression of some heat shock proteins (HSPs) has been reported to suppress the aggregate formation of mutant huntingtin and concurrent cell death. Heat shock transcription factor-1 (HSF 1), a major transcription factor of HSPs, has also been reported to be increased in HD models. However, the exact role of HSF 1 in the pathogenesis of HD has not been clearly elucidated. 3-Nitropropionic acid (3NP), an irreversible inhibitor of the mitochondrial complex II, induces selective damage to the striatum in animals and produces clinical features of HD. To investigate roles of HSF 1 on 3NP-induced oxidative stress, HSF 1 was transiently overexpressed in striatal cells. Expression of HSF 1 significantly attenuated 3NP-induced apoptotic striatal cell death and resulted in increased expression of HSP 70. Furthermore, expression of HSF 1 significantly attenuated 3NP-induced intracellular reactive oxygen species (ROS) generation. Taken together, the present study clearly demonstrates that HSF 1 attenuates 3NP-induced apoptotic striatal cell death and ROS generation, possibly through HSP70 expression, suggesting that HSF 1 might be a valuable therapeutic target in the treatment of HD.
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Hyoja-2, Chunchon, Kangwon 200-701, South Korea.
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Choi
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Om
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Kim
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Chang
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology*; D009574:Nitro Compounds / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D009574:Nitro Compounds; D011422:Propionates; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D013385:Succinate Dehydrogenase; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; C015392:3-nitropropionic acid; D008751:Methylene Blue