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PP2A mediated AMPK inhibition promotes HSP70 expression in heat shock response.

التفاصيل البيبلوغرافية
العنوان: PP2A mediated AMPK inhibition promotes HSP70 expression in heat shock response.
المؤلفون: Ting Wang, Qiujing Yu, Juan Chen, Bo Deng, Lihua Qian, Yingying Le
المصدر: PLoS ONE, Vol 5, Iss 10, p e1000938 (2010)
بيانات النشر: Public Library of Science (PLoS), 2010.
سنة النشر: 2010
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: BACKGROUND: Under stress, AMP-activated protein kinase (AMPK) plays a central role in energy balance, and the heat shock response is a protective mechanism for cell survival. The relationship between AMPK activity and heat shock protein (HSP) expression under stress is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found that heat stress induced dephosphorylation of AMPKα subunit (AMPKα) in various cell types from human and rodent. In HepG2 cells, the dephosphorylation of AMPKα under heat stress in turn caused dephosphorylation of acetyl-CoA carboxylase and upregulation of phosphoenolpyruvate carboxykinase, two downstream targets of AMPK, confirming the inhibition of AMPK activity by heat stress. Treatment of HepG2 cells with phosphatase 2A (PP2A) inhibitor okadaic acid or inhibition of PP2A expression by RNA interference efficiently reversed heat stress-induced AMPKα dephosphorylation, suggesting that heat stress inhibited AMPK through activation of PP2A. Heat stress- and other HSP inducer (CdCl(2), celastrol, MG132)-induced HSP70 expression could be inhibited by AICAR, an AMPK specific activator. Inhibition of AMPKα expression by RNA interference reversed the inhibitory effect of AICAR on HSP70 expression under heat stress. These results indicate that AMPK inhibition under stress contribute to HSP70 expression. Mechanistic studies showed that activation of AMPK by AICAR had no effect on heat stress-induced HSF1 nuclear translocation, phosphorylation and binding with heat response element in the promoter region of HSP70 gene, but significantly decreased HSP70 mRNA stability. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that during heat shock response, PP2A mediated AMPK inhibition upregulates HSP70 expression at least partially through stabilizing its mRNA, which suggests a novel mechanism for HSP induction under stress.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC2948495?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0013096
URL الوصول: https://doaj.org/article/c1ea62c7444e4f92ac131c996058cc9c
رقم الأكسشن: edsdoj.1ea62c7444e4f92ac131c996058cc9c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0013096