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研究発表を行った学会；
・第３４回　日本分子生物学会年会
　２０１１年１２月１３日〜１６日（横浜）

タイトル；Mild electrical stimulation suppresses fat accumulation and increases stress resistance via mitochondrial membrane potential-dependent activation of AMP-activated protein kinase.

発表者；松山　真吾　氏
　　　（熊本大学　大学院生命科学研究部　遺伝子機能応用学分野）
Abstract；
Electrical current has been used as folk medicine and applied as treatment for various diseases. Previously, we showed that co-treatment of mild electrical stimulation (MES) and heat shock (HS) decreased fat accumulation and diabetic phenotypes in high fat-fed mice. Furthermore, pre-treatment with MES and HS prevented liver ischemia/reperfusion injury and gastric ulcer in mice. In these studies, however, the mechanistic details of the effects of MES were unknown. Because MES improves metabolic phenotypes and affects stress response, I hypothesize that MES can impact on mitochondria, which is associated with metabolic dysfunction, cellular stress and damage. MES transiently decreased the mitochondrial membrane potential (MMP) and enhanced AMP-activated kinase (AMPK) phosphorylation in rat skeletal muscle cell L6 and in worms (C.elegans). These effects were inhibited by 5-hydroxydecanoate (5-HD), a specific inhibitor of mitochondrial ATP-sensitive K+ (KATP) channels. More interestingly, pre-treatment with MES of the N2 wild type worms suppressed fat accumulation and increased oxidative/heat stress resistance. Moreover, MES suppressed the expression of SREBP, a master regulator of lipogenesis, and increased the expression of SODs and HSP, which are anti-stress proteins. In contrast, worms bearing the AMPK homologue mutation TG38 did not exhibit MES-induced phenotypes. These results suggested that MES suppresses fat accumulation and increases stress resistance by activating AMPK via decreased MMP. Taken together, the studies elucidated the mechanisms and effects of MES. These finding could promote the use of MES for clinical therapeutic applications for diseases.