期刊
GEROSCIENCE
卷 40, 期 2, 页码 163-176出版社
SPRINGER
DOI: 10.1007/s11357-018-0018-y
关键词
Insulin receptor signaling; Protein chemistry; Mechanistic target of rapamycin; AMP-activated protein kinase
资金
- Veterans Affairs Biomedical Laboratory Research and Development Service [I01BX001340, 5I01BX000926, I01BX002211, II01BX001641]
- NIH [DK50190, HL113303, AG050797]
- American Heart Association [15GRNT25700363]
- Veterans Affairs Senior Research Career Scientist Award [IK6BX003611]
- Nathan Shock Center of Excellence in Basic Biology of Aging [NIH 1P30-AG013319]
Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H2S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H2S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18-19 month-old male C57BL/6 mice to receive 30 mu mol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1 beta, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据