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Chronic hypoxia stress‐induced differential modulation of heat‐shock protein 70 and presynaptic proteins
Author(s) -
Fei Guanghe,
Guo Conghui,
Sun HongShuo,
Feng ZhongPing
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04194.x
Subject(s) - hypoxia (environmental) , heat shock protein , modulation (music) , heat stress , chemistry , differential (mechanical device) , neuroscience , biophysics , microbiology and biotechnology , biology , biochemistry , physics , oxygen , gene , zoology , acoustics , thermodynamics , organic chemistry
Chronic hypoxia exposure can cause neurobehavioral dysfunction, but the underlying cellular and molecular mechanisms remain unclear. Here, we found that adult Lymnaea stagnalis snails maintained in low O 2 (∼ 5%) for 4 days developed slowed reactions to light stimuli, and reduced righting movement. Semiquantitative immunoblotting analyses showed that hypoxia exposure induced increased expression of heat‐shock protein (HSP)70 in ganglion preparations, and suppressed expression of the presynaptic proteins syntaxin I, synaptic vesicle protein 2 (SV2) and synaptotagmin I. Detailed time course analyses showed that an early moderate increase developed within 6 h, preceding a substantial up‐regulation of HSP70 after 4 days; an early reduction of syntaxin I in the first 24 h; a delayed reduction of synaptotagmin I after 4 days; and a biphasic change in SV2. Using a double‐stranded RNA interference approach, we demonstrated that preventing the hypoxia inducible HSP70 enhanced down‐regulation of syntaxin and synaptotagmin, and aggravated motor and sensory suppression. Co‐immunoprecipitation analysis revealed an interaction between HSP70 and syntaxin. We have thus provided the first evidence that early induction of HSP70 by chronic hypoxia is critical for maintaining expression levels of presynaptic proteins. These findings implicate a new molecular mechanism underlying chronic hypoxia‐induced neurobehavioral adaptation and impairment.