title: Silencing of Hsp70 intensifies 6-OHDA-induced apoptosis and Hsp90 upregulation in PC12 cells.
abstract: By the current study, we tried to find out the interactive mechanisms enrolled by Hsp70 and Hsp90 following the 6-hydroxydopamine (6-OHDA)-induced oxidative stress. Of heat shock protein (Hsp) family, we have previously evaluated the effects of Hsp90 gene silencing on in vitro model of Parkinson's disease and its influence on controlling the mechanisms of cell survival. Here, we extended our study to Hsp70 silencing short interfering RNA (siRNA) oligonucleotides, transfected into Pheochromocytoma (PC12) cells with/without exposure to 6-OHDA stress. In order to determine the probable effects of Hsp70 silencing on apoptotic factors, we assessed Bcl2/Bax ratio, nuclear level of PARP, and cleavage of caspase-3 under 6-OHDA stress condition. The results showed deteriorated effect of Hsp70 siRNA on apoptosis in cells exposed to only 6-OHDA. This is, at least in part, in consequence of upregulation of Hsp90, both at messenger RNA (mRNA) and protein levels. These data highlight the critical role of Hsp70 for cell survival under 6-OHDA stress condition. It could be a suggestive issue for supervision of caspase cascades by survival roles of Hsps as Hsp70 silencing resulted in apoptosis phenomenon. Convergence of Hsp70 anti-apoptotic and 6-OHDA pro-apoptotic pathways may explain intensified apoptosis following Hsp70 silencing. In addition, nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor, has been previously studied in detoxification of oxidative stress. For this issue, we tried to elucidate Hsp70 silencing impact on Nrf2, which has been shown to regulate the transcription of Hsp70, unspecifically. Besides, our investigations revealed that Hsp70 siRNA did not affect the level of Nrf2 during 6-OHDA exposure. But, it is still a dealing question and other investigations are needed to have a comprehensive perception of Hsp family signaling functions.
authors.affiliation: Department of Genetic and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. behrangha@yahoo.com.|Department of Applied Cell Science, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran. behrangha@yahoo.com.
authors.forename: Behrang
authors.initials: B
authors.lastname: Alani
authors.affiliation: Department of Genetic and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Salehi
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Sadeghi
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Digaleh
authors.affiliation: Center for Cancer Stem Cell Research, Department of Medicine and Biosystemic Science and Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Siamak
authors.initials: S
authors.lastname: Jabbarzadeh-Tabrizi
authors.affiliation: Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.|Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zare
authors.affiliation: Department of Genetic and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Korbekandi
mesh_terms: D000818:Animals; D051381:Rats; D017209:Apoptosis; D020868:Gene Silencing; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D016716:PC12 Cells; D015854:Up-Regulation; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D016627:Oxidopamine; D051267:NF-E2-Related Factor 2
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