Silencing of Hsp90 chaperone expression protects against 6-hydroxydopamine toxicity in PC12 cells.
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder that has been shown to be associated with oxidative stress. This phenomenon occurs primarily via generation of 6-hydroxydopamine(6-OHDA) in catecholaminergic neurons leading to activation of apoptosis. The 90-kDa heat shock protein (Hsp90) functions as a chaperone in maintaining the functional stability and viability of cells under a transforming pressure. Since Hsp90 binds to inactive transcription factor heat shock factor-1 (HSF-1), inhibition of Hsp90 could activate HSF-1 and transcription of heat shock element containing genes subsequently, like Hsp70 as an anti-apoptotic factor. Our trial of silencing Hsp90 expression through transfection of Hsp90 siRNAs into neuronal PC12 cells being exposed to 6-OHDA resulted in the inhibition of pro-apoptotic factors, Bax, caspase-3, and PARP and upregulation of anti-apoptotic factor, Bcl2. In this manner,our data suggest a protective role for Hsp70 as it was observed to be induced upon Hsp90 knockdown. Furthermore, our results showed that Hsp90 silencing against 6-OHDA-induced oxidative stress may associate with upregulation of nuclear factor-erythroid 2-related factor 2. In summary, we found that silencing of Hsp90 expression leads to induction of cytoprotective pathways which can protect neurons against apoptosis in a PD model.
Behrang
B
Alani
Rasoul
R
Salehi
Payam
P
Sadeghi
Mohammad
M
Zare
Fariba
F
Khodagholi
Ehsan
E
Arefian
Mazdak Ganjalikhani
MG
Hakemi
Hadi
H
Digaleh
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; 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 / Q000633:toxicity; D016716:PC12 Cells; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
D051017:Apoptosis Regulatory Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016627:Oxidopamine