Heat shock protein 70 and AMP-activated protein kinase contribute to 17-DMAG-dependent protection against heat stroke

doi:10.1111/jcmm.12881

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標題:	Heat shock protein 70 and AMP-activated protein kinase contribute to 17-DMAG-dependent protection against heat stroke
作者:	Tsai, Yung-Chieh Lam, Kwok-Keung Peng, Yi-Jen Lee, Yen-Mei Yang, Chung-Yu Tsai, Yi-Ju Yen, Mao-Hsiung Cheng, Pao-Yun
貢獻者:	Chi Mei Med Ctr, Dept Obstet & Gynecol Taipei Med Univ, Dept Med Chia Nan Univ Pharm & Sci, Dept Sport Management Taipei Med Univ, Dept Pharmacol Catholic Mercy Hosp, Dept Anesthesiol Triserv Gen Hosp, Dept Pathol Natl Def Med Ctr Natl Def Med Ctr, Dept Pharmacol Natl Def Med Ctr, Dept Physiol & Biophys
關鍵字:	heat stroke heat shock protein 70 AMP-activated protein kinase 17-DMAG autophagy mortality
日期:	2016-10
上傳時間:	2018-01-18 11:39:47 (UTC+8)
出版者:	Wiley-Blackwell
摘要:	Heat shock protein 70 (Hsp70) preconditioning induces thermotolerance, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a role in the process of autophagy. Here, we investigated whether 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) protected against heat stroke (HS) in rats by up-regulation of Hsp70 and phosphorylated AMPK (pAMPK). To produce HS, male Sprague-Dawley rats were placed in a chamber with an ambient temperature of 42 degrees C. Physiological function (mean arterial pressure, heart rate and core temperature), hepatic and intestinal injury, inflammatory mediators and levels of Hsp70, pAMPK and light chain 3 (LC3B) in hepatic tissue were measured in HS rats or/and rats pre-treated with 17-DMAG. 17-DMAG pre-treatment significantly attenuated hypotension and organ dysfunction induced by HS in rats. The survival time during HS was also prolonged by 17-DMAG treatment. Hsp70 expression was increased, whereas pAMPK levels in the liver were significantly decreased in HS rats. Following pre-treatment with 17-DMAG, Hsp70 protein levels increased further, and pAMPK levels were enhanced. Treatment with an AMPK activator significantly increased the LC3BII/LC3BI ratio as a marker of autophagy in HS rats. Treatment with quercetin significantly suppressed Hsp70 and pAMPK levels and reduced the protective effects of 17-DMAG in HS rats. Both of Hsp70 and AMPK are involved in the 17-DMAG-mediated protection against HS. 17-DMAG may be a promising candidate drug in the clinical setting.
關聯:	Journal of Cellular and Molecular Medicine, v.20 n.10, pp.1889-1897
顯示於類別:	[運動管理系] 期刊論文

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