HSP70 reduces chronic hypoxia-induced neural suppression via regulating expression of syntaxin.
Long-term exposure to modest hypoxia conditions may result in neural dysfunction; however, the involvement of presynaptic proteins has not been tested directly. Here, we reported that adult snails, Lymnaea stagnalis, developed a slow righting movement after placement in low O2 (approximately 5%) for 4 days. Semi-quantitative Western blot analysis showed that hypoxia induced heat shock protein 70 (HSP70) up-regulation and a reduction of syntaxin I. The inducible HSP70 occurs within 6 hours preceding the down-regulation of syntaxin I, suggesting that HSP70 may be involved in regulation of syntaxin expression. Injecting directly double-stranded RNAs (dsRNA) into the center ganglia region, we found that dsRNA HSP70, not the scrambled RNA, prevented the hypoxia-induced HSP70 expression, enhanced the hypoxia-dependent down-regulation of syntaxin I, and aggravated motor suppression. We thus provided the first evidence that early induction of HSP70 by chronic hypoxia is critical for maintaining expression levels of presynaptic proteins and neural function. These findings implicate a new molecular mechanism underlying chronic hypoxia-induced neurobehavioral adaptation and impairment.
Fei
Guanghe
G
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Guo
Conghui
C
Sun
Hong-Shuo
HS
Feng
Zhong-Ping
ZP
D000818:Animals; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D008195:Lymnaea / Q000502:physiology; D009043:Motor Activity; D011187:Posture; D012330:RNA, Double-Stranded / Q000235:genetics; D050827:Syntaxin 1 / Q000235:genetics*
D018840:HSP70 Heat-Shock Proteins; D012330:RNA, Double-Stranded; D050827:Syntaxin 1