Protective Effects of Hydrogen Sulfide in the Ageing Kidney

Hou, Chunmei; Wang, Mingjie; Sun, Chen; Huang, Yong; Jin, Sheng; Mu, Xue-Pan; Chen, Ying; Zhu, Yi‐Chun

doi:10.1155/2016/7570489

Cited by 57 publications

(29 citation statements)

References 34 publications

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“…We administered NaHS by the oral route for 5 months starting at the age of 18-19 months that reversed signaling changes and resulted in these salutary outcomes. Another group of investigators recently reported that intraperitoneal administration of NaHS to 16-month-old mice for 10 weeks stimulates well-known anti-oxidant pathways involving Nrf2 to ameliorate aging-related changes in the kidney (Hou et al 2016); however, that study did not explore the status of H 2 S or signaling mechanisms including IR activation. Our exploration of signaling identified inhibition of AMPK as a key feature of renal aging; administration of H 2 S stimulates AMPK activity that leads to mTORC1 inhibition and reduction in matrix protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide ameliorates aging-associated changes in the kidney

et al. 2018

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Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (HS) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical HS 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 HS 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 μmol/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-1β, 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 HS deficiency. Administration of HS ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.

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Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide ameliorates aging-associated changes in the kidney

et al. 2018

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“…Therefore, we for the first demonstrated that H 2 S prevents Hcy-induced cellular senescence in HT22 cells. It has been confirmed that H 2 S prevents the process of senescence in the endothelium [42], kidney [45,46], vascular [47], heart [48] and brain [43] of mice. Furthermore, increasing the content of endogenous H 2 S by proper diet extends the life span of the aged mice [49,50].…”

Section: Discussionmentioning

confidence: 84%

Hydrogen Sulfide Inhibits Homocysteine-Induced Neuronal Senescence by Up-Regulation of SIRT1

Kang¹,

Li²,

Xie³

et al. 2020

Int. J. Med. Sci.

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Homocysteine (Hcy) accelerates neuronal senescence and induces age-related neurodegenerative diseases. Silence signal regulating factor 1 (SIRT1) prolongs lifespan and takes neuroprotective effects. We have previously demonstrated that hydrogen sulfide (H2S) prevents Hcy-induced apoptosis of neuronal cells and has neuroprotective effect. In the present work, we aimed to investigate whether H2S protects HT22 cells against Hcy-induced neuronal senescence and whether SIRT1 mediates this role of H2S. We found that Hcy induced cellular senescence in HT22 cells, as determined by β-galactosidase staining, expressions of P16 INK4a , P21 CIPL , and trypan blue Staining, which are the markers of cellular senescence. However, sodium hydrosulfide (NaHS, the donor of H2S) significantly reversed Hcy-induced cellular senescence. Interestingly, NaHS not only up-regulated the expression of SIRT1 in HT22 cells but also reversed Hcy-downregulated the expression of SIRT1 in HT22 cells. Furthermore, we found that pretreatment with Sirtinol (an inhibitor of SIRT1) markedly reversed the protection of NaHS against Hcy-induced HT22 cells senescence and apoptosis. Our findings illustrated that H2S protects HT22 cells against Hcy-induced senescence by up-regulating SIRT1.

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“…Klotho –/– mice exhibit enhanced nitrotyrosine levels and reduced levels of antioxidative enzymes, including Mn-SOD in the kidney ( Kimura et al, 2018 ). Additionally, Hou et al (2016) demonstrated that the production of endogenous hydrogen sulfide (H 2 S) in the aging kidney is insufficient. Exogenous H 2 S can reduce renal oxidative stress in aging mice via a mechanism that involves enhanced nuclear translocation of Nrf2 and increased expression of antioxidative enzymes, including Mn-SOD ( Hou et al, 2016 ).…”

Section: Physiological Significance Of Manganese Superoxide Dismutasementioning

confidence: 99%

Manganese Superoxide Dismutase Dysfunction and the Pathogenesis of Kidney Disease

Kitada

Ogura

et al. 2020

Front. Physiol.

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The mitochondria are a major source of reactive oxygen species (ROS). Superoxide anion (O 2 •– ) is produced by the process of oxidative phosphorylation associated with glucose, amino acid, and fatty acid metabolism, resulting in the production of adenosine triphosphate (ATP) in the mitochondria. Excess production of reactive oxidants in the mitochondria, including O 2 •– , and its by-product, peroxynitrite (ONOO – ), which is generated by a reaction between O 2 •– with nitric oxide (NO • ), alters cellular function via oxidative modification of proteins, lipids, and nucleic acids. Mitochondria maintain an antioxidant enzyme system that eliminates excess ROS; manganese superoxide dismutase (Mn-SOD) is one of the major components of this system, as it catalyzes the first step involved in scavenging ROS. Reduced expression and/or the activity of Mn-SOD results in diminished mitochondrial antioxidant capacity; this can impair the overall health of the cell by altering mitochondrial function and may lead to the development and progression of kidney disease. Targeted therapeutic agents may protect mitochondrial proteins, including Mn-SOD against oxidative stress-induced dysfunction, and this may consequently lead to the protection of renal function. Here, we describe the biological function and regulation of Mn-SOD and review the significance of mitochondrial oxidative stress concerning the pathogenesis of kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), with a focus on Mn-SOD dysfunction.

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Protective Effects of Hydrogen Sulfide in the Ageing Kidney

Cited by 57 publications

References 34 publications

Hydrogen sulfide ameliorates aging-associated changes in the kidney

Hydrogen sulfide ameliorates aging-associated changes in the kidney

Hydrogen Sulfide Inhibits Homocysteine-Induced Neuronal Senescence by Up-Regulation of SIRT1

Manganese Superoxide Dismutase Dysfunction and the Pathogenesis of Kidney Disease

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