Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits

被引：433

作者：

Hine, Christopher ^{[1
]}

Harputlugil, Eylul ^{[1
]}

Zhang, Yue ^{[1
]}

Ruckenstuhl, Christoph ^{[5
]}

Lee, Byung Cheon ^{[2
]}

Brace, Lear ^{[1
]}

Longchamp, Alban ^{[1
,3
,4
]}

Trevino-Villarreal, Jose H. ^{[1
]}

Mejia, Pedro ^{[1
]}

Ozaki, C. Keith ^{[3
,4
]}

Wang, Rui ^{[7
]}

Gladyshev, Vadim N. ^{[2
]}

Madeo, Frank ^{[5
,6
]}

Mair, William B. ^{[1
]}

Mitchell, James R. ^{[1
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA

[5] Graz Univ, Inst Mol Biosci, NAWI Graz, A-8010 Graz, Austria

[6] BioTechMed Graz, A-8010 Graz, Austria

[7] Lakehead Univ, Dept Biol, Thunder Bay, ON P7B 5E1, Canada

来源：

CELL | 2015年 / 160卷 / 1-2期

基金：

奥地利科学基金会; 加拿大健康研究院;

关键词：

EXTENDS LIFE-SPAN; CALORIC RESTRICTION; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; STRESS RESISTANCE; OXIDATIVE STRESS; METHIONINE; MICE; LONGEVITY; INJURY;

D O I：

10.1016/j.cell.2014.11.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 gamma-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.

引用

页码：132 / 144

页数：13

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