Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury

Wu, Dongdong; Wang, Jun; Li, Hui; Xue, Mengzhou; Ji, Ailing; Li, Yanzhang

doi:10.1155/2015/186908

Cited by 122 publications

(88 citation statements)

References 191 publications

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“…H 2 S is involved in the regulation of renal function and increases urinary sodium excretion through tubular and vascular actions in the kidney, and it can also alleviate renal IRI via antioxidant, anti-apoptotic, and anti-inflammatory effects, which the exact opposite of the roles of urinary protein. BUN and SCR are associated with the role of SOD in renal injury, implying that H 2 S may inhibit urinary protein, BUN and SCR to increase SOD [25]. Leelahavanichkul et al have suggested that the level of SCR in animals with SR deficiency was half that of control animals, indicating better-maintained kidney function [32].…”

Section: Discussionmentioning

confidence: 99%

“…A study by Ji et al has demonstrated that exogenous H 2 S post-conditioning can successfully prevent the rat heart from experiencing IRI [24]. In addition, H 2 S is regarded as an endogenous signaling molecule which exerts cardio-protection against MIRI in cardiac myocytes and also known as a powerful neuro-protective agent in the central nervous system [25, 26]. Therefore, the present study was conducted to explore the effects of the exogenous H 2 S-mediated SR-A signaling pathway on renal IRI by regulating ER stress-induced autophagy in rats.…”

Section: Introductionmentioning

confidence: 99%

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Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Ling¹,

Yu²,

Wang³

et al. 2017

Cell Physiol Biochem

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Objective: This study aims to explore the effects of the exogenous hydrogen sulfide (H₂S)-mediated scavenger receptor A (SR-A) signaling pathway on renal ischemia/reperfusion injury (IRI) by regulating endoplasmic reticulum (ER) stress-induced autophagy in rats. Methods: A total of 48 normal Sprague-Dawley (SD) rats and SR-A knockout rats were selected and divided into six groups (n = 8): wild-type (WT) + sham, WT + ischemia-reperfusion (I/R), WT + I/R + NaHS, SR-A^-/- + sham, SR-A^-/- + I/R and SR-A^-/- + I/R + NaHS. The concentrations of urinary protein, blood urea nitrogen (BUN), serum creatinine (SCR), malondialdehyde (MDA) and H₂S in renal tissue were detected. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of IL-6, TGF-β, SR-A, LC3I, LC3II, P62, PERK, ATF6 and IRE1 pathway-related genes. A TUNEL assay was used to detect cell apoptosis. Electron microscopy was applied to observe the structure of renal autophagosomes. Results: Compared with the WT + sham group, in the rates of the WT + I/R group, the urine volume, urinary protein, BUN, SCR and MDA concentrations, the mRNA and protein expression of IL-6, TGF-β, LC3II/I, and ER stress pathway-related genes, the cell apoptosis index, and the number of autophagosomes were significantly increased 24 h after I/R, while P62 and SR-A protein expression and SOD and H₂S concentrations were significantly decreased (all P < 0.05). The levels of renal injury, autophagy and ER stress pathway-related genes were decreased in the WT + I/R + NaHS group but were increased in the SR-A^-/- + I/R group relative to the WT + I/R group. No significant differences were observed in the urine volume; the concentrations of urinary protein, BUN, SCR and MDA; the SOD activity; the mRNA and protein expression of IL-6, TGF-β, SR-A, GRP78, SR-A, GPR94, ATF4, IRE1, XBP1, ATF6, and eIF2α; the cell apoptosis index; or the number of autophagosomes in rats of the SR-A^-/- + I/R and SR-A^-/- + I/R + NaHS groups (all P > 0.05). Conclusion: These results demonstrate that the exogenous H₂S-mediated SR-A signaling pathway reduces renal IRI injury by up-regulating ER stress-induced autophagy in rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Ling¹,

Yu²,

Wang³

et al. 2017

Cell Physiol Biochem

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“…Hydrogen sulfide (H2S) is endogenously produced by animal cells that has various roles in cellular signaling (Li et al, 2011). Exposure to low levels of exogenous H2S induces a suspendedanimation like state in rodents that is associated with increased survival in whole-body hypoxia and improved outcome in models of ischemia-reperfusion injury (Blackstone and Roth, 2007;Jensen et al, 2017;Wu et al, 2015). However, H2S is also a common environmental toxin, and human exposure is associated with respiratory and neurological dysfunction (Malone Rubright et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

C. elegans RHY-1 and CYSL-1 act independently of HIF-1 to promote survival in hydrogen sulfide

Horsman

Heinis

Miller

2019

Preprint

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Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, exposure to exogenous H2S can be toxic, perhaps due to unregulated activation of endogenous H2S signaling pathways. We use the nematode C. elegans to define mechanisms that mediate the physiological effects of H2S in animals. We have previously shown that in C. elegans the hypoxia inducible factor (hif-1) coordinates the initial transcriptional response to H2S and is essential to survive exposure to low concentrations of H2S. In this study, we performed a forward genetic screen to identify mutations that suppress the lethality of hif-1 mutant animals in H2S. The mutations we recovered do not suppress embryonic lethality or reproductive arrest of hif-1 mutant animals in hypoxia, nor can they improve viability of hif-1 mutant animals exposed to hydrogen cyanide, indicating that these are specific for H2S. We found that the hif-1 suppressor mutations activate the skn-1/Nrf2 transcription factor. Activation of SKN-1 by hif-1 suppressor mutations increased the expression of a subset of H2S-responsive genes, consistent with our previous finding that skn-1 plays a role in the transcriptional response to H2S. Using transgenic rescue, we show a single gene, rhy-1, alone is sufficient to protect hif-1 mutant animals in H2S. Our data indicate that RHY-1 acts in concert with CYSL-1, an orthologue of human cystathionine b-synthase, to promote survival in H2S. The rhy-1 gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our studies reveal a novel function of RHY-1, which is independent of hif-1, that protects against toxic effects of H2S.

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“…Chronic 21 exposure to relatively low concentrations of environmental H2S in humans has been 22 associated with neurological, respiratory, and cardiovascular dysfunction (Kilburn and 23 Warshaw, 1995;Richardson, 1995;Bates et al, 2002). However, transient exposure to 24 low H 2 S has also been shown to improve outcome in many mammalian models of 25 ischemia-reperfusion injury (Bos et al, 2015;Wu et al, 2015). It is possible that the 26 biological effects of exogenous H 2 S exposure, both beneficial and detrimental, result 27 from activation of pathways that are normally regulated by endogenous H 2 S. 28 C. elegans is an excellent system to define physiological responses to exogenous 29 H2S.…”

Section: Introduction 16mentioning

confidence: 99%

C. elegansHIF-1 is broadly required for survival in hydrogen sulfide

Topalidou

Miller

2017

Preprint

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1Hydrogen sulfide is common in the environment, and is also endogenously produced 2 by animal cells. Although hydrogen sulfide is often toxic, exposure to low levels of 3 hydrogen sulfide improves outcome in a variety of mammalian models of ischemia-4 reperfusion injury. In Caenorhabditis elegans, the initial transcriptional response to 5 hydrogen sulfide depends on the hif-1 transcription factor, and hif-1 mutant animals die 6 when exposed to hydrogen sulfide. In this study, we use rescue experiments to identify 7 tissues in which hif-1 is required to survive exposure to hydrogen sulfide. We find that 8 expression of hif-1 from the unc-14 promoter is sufficient to survive hydrogen sulfide. 9Although unc-14 is generally considered to be a pan-neuronal promoter, we show that it 10 is active in many non-neuronal cells as well. Using other promoters, we show that pan-11 neuronal expression of hif-1 is not sufficient to survive exposure to hydrogen sulfide. 12Our data suggest that hif-1 is required in many different tissues to direct the essential 13 response to hydrogen sulfide.

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Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury

Cited by 122 publications

References 191 publications

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

C. elegans RHY-1 and CYSL-1 act independently of HIF-1 to promote survival in hydrogen sulfide

C. elegansHIF-1 is broadly required for survival in hydrogen sulfide

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