内源性硫化氢的产生对饮食限制的益处至关重要。
Endogenous hydrogen sulfide production is essential for dietary restriction benefits.
作者信息
Hine Christopher, Harputlugil Eylul, Zhang Yue, Ruckenstuhl Christoph, Lee Byung Cheon, Brace Lear, Longchamp Alban, Treviño-Villarreal Jose H, Mejia Pedro, Ozaki C Keith, Wang Rui, Gladyshev Vadim N, Madeo Frank, Mair William B, Mitchell James R
机构信息
Department of Genetics and Complex Diseases, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Institute for Molecular Biosciences, NAWI Graz, University of Graz, Graz 8010, Austria.
出版信息
Cell. 2015 Jan 15;160(1-2):132-44. doi: 10.1016/j.cell.2014.11.048. Epub 2014 Dec 23.
Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine γ-lyase (CGL), resulting in increased hydrogen sulfide (H2S) production and protection from hepatic ischemia reperfusion injury. SAA supplementation, mTORC1 activation, or chemical/genetic CGL inhibition reduced H2S production and blocked DR-mediated stress resistance. In vitro, the mitochondrial protein SQR was required for H2S-mediated protection during nutrient/oxygen deprivation. Finally, TSP-dependent H2S production was observed in yeast, worm, fruit fly, and rodent models of DR-mediated longevity. Together, these data are consistent with evolutionary conservation of TSP-mediated H2S as a mediator of DR benefits with broad implications for clinical translation. PAPERFLICK:
无营养不良的饮食限制（DR）涵盖了众多具有重叠益处（包括延长寿命和抗应激能力）的方案，但统一的营养和分子机制仍然难以捉摸。在DR介导的抗应激小鼠模型中，我们发现限制硫氨基酸（SAA）会增加转硫途径（TSP）酶胱硫醚γ-裂解酶（CGL）的表达，从而导致硫化氢（H2S）生成增加，并对肝脏缺血再灌注损伤起到保护作用。补充SAA、激活mTORC1或化学/基因抑制CGL会减少H2S生成，并阻断DR介导的抗应激能力。在体外，线粒体蛋白SQR是营养/氧气剥夺期间H2S介导的保护所必需的。最后，在DR介导的长寿酵母、蠕虫、果蝇和啮齿动物模型中观察到了TSP依赖性H2S生成。总之，这些数据与TSP介导的H2S作为DR益处的介质的进化保守性一致，对临床转化具有广泛影响。PAPERFLICK:
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