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Hydrogen Sulfide and Endoplasmic Reticulum Stress: A Potential Therapeutic Target for Central Nervous System Degeneration Diseases.

ABSTRACT: There are three members of the endogenous gas transmitter family. The first two are nitric oxide and carbon monoxide, and the third newly added member is hydrogen sulfide (H2S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, learning, and memory. The cystathionine ?-synthase (CBS), 3-mercaptopyruvate sulfur transferase acts together with cysteine aminotransferase (3-MST/CAT), cystathionine ?-lyase (CSE), and 3-mercaptopyruvate sulfur transferase with D-amino acid oxidase (3-MST/DAO) pathways are involved in the enzymatic production of H2S. More and more researches focus on the role of H2S in the central nervous system (CNS), and H2S plays a significant function in neuroprotection processes, regulating the function of the nervous system as a signaling molecule in the CNS. Endoplasmic reticulum stress (ERS) and protein misfolding in its mechanism are related to neurodegenerative diseases. H2S exhibits a wide variety of cytoprotective and physiological functions in the CNS degenerative diseases by regulating ERS. This review summarized on the neuroprotective effect of H2S for ERS played in several CNS diseases including Alzheimer's disease, Parkinson's disease, and depression disorder, and discussed the corresponding possible signaling pathways or mechanisms as well.

SUBMITTER: Zhong H

PROVIDER: S-EPMC7240010 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hydrogen Sulfide and Endoplasmic Reticulum Stress: A Potential Therapeutic Target for Central Nervous System Degeneration Diseases.

Zhong Huimin H Yu Huan H Chen Junjue J Sun Jun J Guo Lei L Huang Ping P Zhong Yisheng Y

Frontiers in pharmacology 20200514

There are three members of the endogenous gas transmitter family. The first two are nitric oxide and carbon monoxide, and the third newly added member is hydrogen sulfide (H<sub>2</sub>S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, learning, and memory. The cystathionine <i>β</i>-synthase (CBS), 3-mercaptopyruvate sulfur transferase acts together with cysteine aminotransferase (3-MST/CAT), cystathioni ...[more]

PMID: 32477150

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Project description:The aim of the present study was to explore the effect of exogenous hydrogen sulphide (H2S) on endoplasmic reticulum (ER) stress (ERS) in a rat model of hepatic ischemia/reperfusion (I/R) injury. A total of 48 Sprague-Dawley rats were randomly divided into four groups (n=12/group) as follows: Sham, I/R, I/R preceded by NaHS (I/R-NaHS) and I/R preceded by L-C-propargylglycine (PAG), a H2S inhibitor (I/R-PAG). With the exception of the sham group, the rats in the other groups were subjected to 30 min hepatic warm ischemia followed by reperfusion for 6 or 12 h. Hepatic function was evaluated by serum concentrations of alanine aminotransferase (ALT). Apoptosis of hepatic cells was assessed by TUNEL staining and measurement of caspase-12 expression. The expression levels of ERS-associated proteins and mRNAs of pancreatic ER eukaryotic translation initiation factor-2a kinase (PERK), activating transcription factor-6 (ATF6), glucose-regulated protein (GRP) 78, TNF-receptor-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and caspase-12 were also measured by western blotting and reverse transcription-quantitative PCR. The serum concentrations of ALT in the I/R and I/R-PAG groups were found to be significantly higher compared with those in the sham and I/R-NaHS groups after 6 h of reperfusion; in addition, the ALT level returned to normal in the I/R group, while it increased further in the I/R-PAG group after 12 h of reperfusion. A higher cell apoptosis rate was observed in the I/R and I/R-PAG groups and the highest cell apoptosis rate was observed in the I/R-PAG group; correspondingly, the expression of caspase-12 was increased in the I/R and I/R-PAG groups. H2S appeared to significantly attenuate hepatic I/R-induced ERS response, as indicated by the decreased expression of ATF6, PERK, GRP78, TRAF2 and CHOP. Endogenous H2S may serve a hepatoprotective function after I/R, and inhibition of endogenous H2S results in aggravation of I/R damage. Exogenous H2S was shown to inhibit ERS-related gene expression, leading to suppression of inflammatory reaction and improvement of I/R damage. Therefore, exogenous H2S has therapeutic potential to alleviate hepatic I/R injury.

Dataset Information

Hydrogen Sulfide and Endoplasmic Reticulum Stress: A Potential Therapeutic Target for Central Nervous System Degeneration Diseases.

Publications

Hydrogen Sulfide and Endoplasmic Reticulum Stress: A Potential Therapeutic Target for Central Nervous System Degeneration Diseases.

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