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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31011


    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
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