Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats

Jiang, Wen-Wu; Huang, Biao; Han, Yang; Deng, Lv-Hong; Wu, Lixiang

doi:10.1002/2211-5463.12301

Cited by 58 publications

(31 citation statements)

References 32 publications

(37 reference statements)

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“…However, in our model OGD did not affect formation of autophagosomes and protein levels of ATG7 and LC3. Similar to our results, Jiang et al [ 67 ] observed a reduction in the protein level of NUP62 and an increase in the protein level of BECN1 in cellular (PC12 cells) and animal (middle cerebral artery occlusion) models of ischemia. In line with our study, Perez-Rodriguez et al [ 68 ] did not notice a change in the protein level of ATG7 in hippocampal slices subjected to OGD.…”

Section: Discussionsupporting

confidence: 92%

The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling

et al. 2019

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There are no studies examining the effects of 3,3′-diindolylmethane (DIM) in neuronal cells subjected to ischemia. Little is also known about the roles of apoptosis and autophagy as well as AhR and ERα signaling and HDACs in DIM action. We demonstrated for the first time the strong neuroprotective capacity of DIM in mouse primary hippocampal cell cultures exposed to ischemia at early and later stages of neuronal development. The protective effects of DIM were mediated via inhibition of ischemia-induced apoptosis and autophagy that was accompanied by a decrease in AhR/CYP1A1 signaling and an increase in HDAC activity. DIM decreased the levels of pro-apoptotic factors, i.e., Fas, Caspase-3, and p38 mitogen-activated protein kinase (MAPK). DIM also reduced the protein levels of autophagy-related Beclin-1 (BECN1) and microtubule-associated proteins 1A/1B light chain (LC3), partially reversed the ischemia-induced decrease in Nucleoporin 62 (NUP62) and inhibited autophagosome formation. In addition, DIM completely reversed the ischemia-induced decrease in histone deacetylase (HDAC) activity in hippocampal neurons. Although DIM inhibited AhR/CYP1A1 signaling, it did not influence the protein expression levels of ERα and ERα-regulated CYP19A1 which are known to be controlled by AhR. This study demonstrated for the first time, that the neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy and depends on AhR/CYP1A1 signaling and HDAC activity, thus creating the possibility of developing new therapeutic strategies that target neuronal degeneration at specific molecular levels.

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Section: Discussionsupporting

confidence: 92%

The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling

et al. 2019

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“…ATG proteins and vacuoles increase concomitantly with the apoptotic markers within dying neurons. This supports the hypothesis for a detrimental role of ATG in post-ischemic cell death [ 80 , 84 , 85 , 86 , 87 ].…”

Section: The Autophagy Pathway As a Hot Topic In Brain Hypoperfusisupporting

confidence: 88%

Ambiguous Effects of Autophagy Activation Following Hypoperfusion/Ischemia

Ferrucci

Biagioni

Ryskalin

et al. 2018

IJMS

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Autophagy primarily works to counteract nutrient deprivation that is strongly engaged during starvation and hypoxia, which happens in hypoperfusion. Nonetheless, autophagy is slightly active even in baseline conditions, when it is useful to remove aged proteins and organelles. This is critical when the mitochondria and/or proteins are damaged by toxic stimuli. In the present review, we discuss to that extent the recruitment of autophagy is beneficial in counteracting brain hypoperfusion or, vice-versa, its overactivity may per se be detrimental for cell survival. While analyzing these opposite effects, it turns out that the autophagy activity is likely not to be simply good or bad for cell survival, but its role varies depending on the timing and amount of autophagy activation. This calls for the need for an appropriate autophagy tuning to guarantee a beneficial effect on cell survival. Therefore, the present article draws a theoretical pattern of autophagy activation, which is hypothesized to define the appropriate timing and intensity, which should mirrors the duration and severity of brain hypoperfusion. The need for a fine tuning of the autophagy activation may explain why confounding outcomes occur when autophagy is studied using a rather simplistic approach.

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“…All the stained brain slices were photographed subsequently to delineate the area of infarct size using Image J, version 1.6 (National Institutes of Health, Bethesda, MD, USA). As described previously ( 9 ), the percentage of infarction volume was determined by normalizing the whole brain.…”

Section: Methodsmentioning

confidence: 99%

“…Hydrogen sulfide (H 2 S) is regarded as the third endogenous gasotransmitter ( 6 ), following carbon monoxide (CO) and nitric oxide (NO). Accumulated evidence indicates that H 2 S plays a much more active and important role against ischemia/reperfusion (I/R) injury, such as kidney I/R injury ( 7 ), myocardial I/R injury ( 8 ), and cerebral I/R injury ( 9 ). Endogenous H 2 S is mainly produced from L-cysteine (L-Cys) in intracytoplasm by cystathionine r-lyase (CSE), cystathionine β-synthase (CBS), and β-mercaptopyruvic acid in mitochondria by 3-mercaptopyruvate sulfurtransferase (3-MST) ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Vascular Protection of Hydrogen Sulfide on Cerebral Ischemia/Reperfusion Injury in Rats

Wen

Wang

et al. 2018

Front. Neurol.

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This study was undertaken to demonstrate the vascular protection of exogenous and endogenous hydrogen sulfide (H2S) on cerebral ischemia/reperfusion (I/R) injury. The effect of H2S on cerebrovascular dysfunction in middle cerebral artery (MCA) and neuronal damage were measured after cerebral I/R induced by transient middle cerebral artery occlusion (MCAO) in cystathionine c-lyase (CSE) knockdown and wild-type rats. The effect of sodium hydrosulfide (NaHS, donor of exogenous H2S), L-cysteine (L-Cys, substrate of endogenous H2S), and endothelium cells on the responses of isolated MCA derived from non-ischemic rats was also evaluated to assess the underlying mechanism of H2S-mediate cerebral vasodilation. The results revealed that the contraction and dilation of MCA profoundly decreased after cerebral I/R. The vascular dysfunction became more grievous in CSE knockdown rats than in wild-type rats. Interestingly, this vascular dysfunction was significantly alleviated by NaHS supplementation. Moreover, both NaHS and L-cysteine could induce remarkable relaxation in the isolated MCA, which was eliminated by co-application of potassium channel blockers ChTx and Apamin, or endothelial removal. By contrast, adding endothelium cells cultured in vitro together with ACh into the luminal perfusate could mimic non-NO and non-PGI2 relaxation in endothelium-denuded MCA, once CSE was knocked down from endothelium cells, and its effect on vasorelaxation was abolished. Furthermore, the indexes of neuronal injury were measured after cerebral I/R to confirm the neuroprotection of H2S, and we found that the neurological scores, cerebral infarction volume, brain water content, malondialdehyde content, and serum lactate dehydrogenase activity (a marker of cellular membrane integrity) were significantly higher in CSE knockdown rats than in normal control rats. It is not surprising that NaHS could alleviate the cerebral injury. These findings revealed that H2S has a protective effect on cerebral I/R injury via its upregulation of the endothelium-dependent contraction and dilation function of cerebral vessels, which may be related to activating potassium channel.

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Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats

Cited by 58 publications

References 32 publications

The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling

The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling

Ambiguous Effects of Autophagy Activation Following Hypoperfusion/Ischemia

Vascular Protection of Hydrogen Sulfide on Cerebral Ischemia/Reperfusion Injury in Rats

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