Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury

Bos, Eelke M.; Leuvenink, Henri G. D.; Snijder, Pauline M.; Kloosterhuis, Niels J.; Hillebrands, Jan-Luuk; Leemans, Jaklien C.; Florquin, Sandrine; Goor, Harry van

doi:10.1681/asn.2008121269

Cited by 150 publications

(135 citation statements)

References 18 publications

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“…Although H 2 S is very toxic at high concentrations, it is produced at low concentrations by the degradation of cysteine or homocysteine by CGL or CBS, and acts in the vasculature and the brain as a signaling molecule, reducing blood pressure (Yang et al., 2008), and preventing neurodegeneration (Paul & Snyder, 2012). Furthermore, exogenous H 2 S can also extend the lifespan of worms (Miller & Roth, 2007) and prevent kidney injury in some experimental models (Bos et al., 2009; Holwerda et al., 2014). Thus, it is apparent that H 2 S has a protective role in tissues in a number of species.…”

Section: Discussionmentioning

confidence: 99%

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

et al. 2018

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SummaryExtending healthy lifespan is an emerging issue in an aging society. This study was designed to identify a dietary method of extending lifespan, promoting renoprotection, and preventing muscle weakness in aged mice, with a focus on the importance of the balance between dietary essential (EAAs) and nonessential amino acids (NEAAs) on the dietary restriction (DR)‐induced antiaging effect. Groups of aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or EAAs. Simple DR significantly extended lifespan and ameliorated age‐related kidney injury; however, the beneficial effects of DR were canceled by recovering dietary EAA but not NEAA. Simple DR prevented the age‐dependent decrease in slow‐twitch muscle fiber function but reduced absolute fast‐twitch muscle fiber function. DR‐induced fast‐twitch muscle fiber dysfunction was improved by recovering either dietary NEAAs or EAAs. In the ad libitum‐fed and the DR plus EAA groups, the renal content of methionine, an EAA, was significantly higher, accompanied by lower renal production of hydrogen sulfide (H2S), an endogenous antioxidant. Finally, removal of methionine from the dietary EAA supplement diminished the adverse effects of dietary EAA on lifespan and kidney injury in the diet‐restricted aged mice, which were accompanied by a recovery in H2S production capacity and lower oxidative stress. These data imply that a dietary approach could combat kidney aging and prolong lifespan, while preventing muscle weakness, and suggest that renal methionine metabolism and the trans‐sulfuration pathway could be therapeutic targets for preventing kidney aging and subsequently promoting healthy aging.

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Section: Discussionmentioning

confidence: 99%

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

et al. 2018

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“…3,5,6,35,36 H 2 S is known for its proangiogenic, antihypertensive, and organ protective properties. 28,37,38 In this study, we investigated the effects of exogenously administrated H 2 S in a rat model for severe endothelial dysfunction, induced by overexpression of sFlt1. As previously described, elevation of plasma sFlt1 by adenoviral overexpression resulted in hypertension, proteinuria, and glomerular endotheliosis.…”

Section: Discussionmentioning

confidence: 99%

“…[28][29][30][31] The proangiogenic effect of H 2 S was first described by Cai et al, who showed that an exogenously administrated H 2 S donor (sodium hydrosulfide [NaHS]) promoted proliferation, migration, and tube-like structure formation in endothelial cells in vitro. 32 In vivo, it was demonstrated that H 2 S is a proangiogenic factor in a model of hind limb ischemia.…”

mentioning

confidence: 99%

Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

Holwerda¹,

Burke²,

Faas³

et al. 2014

Journal of the American Society of Nephrology

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Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein, is elevated in kidney diseases and contributes to the development of preeclampsia. Hydrogen sulfide is a vasorelaxant and proangiogenic gas with therapeutic potential in several diseases. Therefore, we evaluated the potential therapeutic effect and mechanisms of action of hydrogen sulfide in an animal model of sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis created by adenovirus-mediated overexpression of sFlt1 in Sprague-Dawley rats. We injected sFlt1-overexpressing animals intraperitoneally with the hydrogen sulfide-donor sodium hydrosulfide (NaHS) (50 mmol/kg, twice daily) or vehicle (n=7 per group). Treatment with NaHS for 8 days significantly reduced sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis. Measurement of plasma protein concentrations with ELISA revealed a reduction of free plasma sFlt1 and an increase of free plasma vascular endothelial growth factor (VEGF) after treatment with NaHS. Renal VEGF-A mRNA expression increased significantly with NaHS treatment. In vitro, NaHS was proangiogenic in an endothelial tube assay and attenuated the antiangiogenic effects of sFlt1. Stimulation of podocytes with NaHS resulted in both short-term VEGF release (120 minutes) and upregulation of VEGF-A mRNA levels (24 hours). Furthermore, pretreatment of mesenteric vessels with a VEGF receptor 2-neutralizing antibody significantly attenuated NaHS-induced vasodilation. These results suggest that hydrogen sulfide ameliorates sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis in rats by increasing VEGF expression. Further studies are warranted to evaluate the role of hydrogen sulfide as a novel therapeutic agent for vascular disorders such as preeclampsia.

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“…H 2 S also confers cytoprotection via suppression of inflammation (17) and by protecting mitochondrial function and integrity (17,18). Decreased levels of H 2 S in brain tissue are associated with neurodegenerative age-related diseases such as Parkinson's (19), and administration of H 2 S has been shown protective in experimental models for this disease (20)(21)(22).…”

Section: Overexpression Of Cystathionine γ-Lyase Suppresses Detrimentmentioning

confidence: 99%

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Snijder

Baratashvili

Grzeschik

et al. 2015

Mol Med

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Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show that overexpression of cystathionine γ-lyase, a central enzyme in cysteine metabolism, is protective in a Drosophila model for SCA3. SCA3 flies show eye degeneration, increased oxidative stress, insoluble protein aggregates, reduced levels of protein persulfidation and increased activation of the innate immune response. Overexpression of Drosophila cystathionine γ-lyase restores protein persulfidation, decreases oxidative stress, dampens the immune response and improves SCA3-associated tissue degeneration. Levels of insoluble protein aggregates are not altered; therefore, the data implicate a modifying role of cystathionine γ-lyase in ameliorating the downstream consequence of protein aggregation leading to protection against SCA3-induced tissue degeneration. The cystathionine γ-lyase expression is decreased in affected brain tissue of SCA3 patients, suggesting that enhancers of cystathionine γ-lyase expression or activity are attractive candidates for future therapies.

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Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury

Cited by 150 publications

References 18 publications

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

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