Mild electrical stimulation increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway in C. elegans.
Mild electrical stimulation increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway in C. elegans.
复制标题
DOI：
10.1371/journal.pone.0114690
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kai H
中科院分区：
文献类型：
--
作者：
Matsuyama S;Moriuchi M;Suico MA;Yano S;Morino-Koga S;Shuto T;Yamanaka K;Kondo T;Araki E;Kai H
生理强度的电流已被用作多种疾病的治疗方法。我们的几项工作表明，0.1 毫秒脉冲宽度的温和电刺激 (MES) 对生物体具有积极影响。但是，尽管越来越多的证据表明 MES 的有益作用，但它对个体动物的影响及其分子基础却知之甚少，也很少进行研究。在这里，我们主要利用秀丽隐杆线虫这种强大的遗传模型生物来研究 MES 对个体动物的影响及其机制。有趣的是，MES 提高了野生型 N2 线虫的抗逆性并抑制了过多的脂肪积累，但在 AMPK/AAK-2 和 LKB1/PAR-4 突变线虫中则不然。 MES促进转录因子DAF-16和SKN-1的核定位，从而增加抗应激基因的表达，而MES抑制SBP-1的核定位并抑制脂肪生成基因的表达。此外，我们发现 MES 诱导秀丽隐杆线虫和几种哺乳动物细胞系中 LKB1/PAR4-AMPK/AAK2 通路的激活。 MES 轻微短暂降低线粒体膜电位和细胞 ATP 水平，导致 LKB1-AMPK 信号通路激活。我们首先从基因角度证明了 MES 通过激活 LKB1-AMPK 信号通路发挥有益作用，例如抗应激和抑制多余脂肪积累。
Electrical current at physiological strength has been applied as a therapeutic approach for various diseases. Several of our works showed that mild electrical stimulation (MES) at 0.1-ms pulse width has positive impact on organisms. But despite the growing evidence of the beneficial effects of MES, its effects on individual animals and the molecular underpinnings are poorly understood and rarely studied. Here, we examined the effects of MES on individual animal and its mechanisms by mainly using Caenorhabditis elegans, a powerful genetic model organism. Interestingly, MES increased stress resistance and suppressed excess fat accumulation in wild-type N2 worms but not in AMPK/AAK-2 and LKB1/PAR-4 mutant worms. MES promoted the nuclear localization of transcription factors DAF-16 and SKN-1 and consequently increased the expression of anti-stress genes, whereas MES inhibited the nuclear localization of SBP-1 and suppressed the expression of lipogenic genes. Moreover, we found that MES induced the activation of LKB1/PAR4-AMPK/AAK2 pathway in C. elegans and in several mammalian cell lines. The mitochondrial membrane potential and cellular ATP level were slightly and transiently decreased by MES leading to the activation of LKB1-AMPK signaling pathway. Together, we firstly and genetically demonstrated that MES exerts beneficial effects such as stress resistance and suppression of excess fat accumulation, via activation of LKB1-AMPK signaling pathway.
登录
查看更多内容
影响因子：
3.9
作者：
Gowans GJ;Hardie DG
通讯作者：
Hardie DG
影响因子：
7.7
作者：
Kondo T;Sasaki K;Matsuyama R;Morino-Koga S;Adachi H;Suico MA;Kawashima J;Motoshima H;Furukawa N;Kai H;Araki E
通讯作者：
Araki E
影响因子：
3.7
作者：
Morino, Saori;Kondo, Tatsuya;Sasaki, Kazunari;Adachi, Hironori;Suico, Mary Ann;Sekimoto, Erika;Matsuda, Tomoko;Shuto, Tsuyoshi;Araki, Eiichi;Kai, Hirofumi
通讯作者：
Kai, Hirofumi
轻度电刺激和热休克可改善阿尔波特综合征小鼠模型中进行性蛋白尿和肾脏炎症。
影响因子：
3.7
作者：
Koga T;Kai Y;Fukuda R;Morino-Koga S;Suico MA;Koyama K;Sato T;Shuto T;Kai H
通讯作者：
Kai H
影响因子：
7.4
作者：
Ainsworth, L;Budelier, K;Sluka, KA
通讯作者：
Sluka, KA