Golgi Stress Response, Hydrogen Sulfide Metabolism, and Intracellular Calcium Homeostasis
- 20 March 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 32 (9), 583-601
- https://doi.org/10.1089/ars.2019.7824
Abstract
Aims: The physiological and pathological importance of hydrogen sulfide (H2S) as a novel gasotransmitter has been widely recognized. Cystathionine gamma-lyase (CSE) is one of the major H2S-producing enzymes and it regulates diverse functions in connection with intracellular calcium (Ca2+). The aim of this study is to examine the role of H2S in Golgi stress-related cell injury and skeletal muscle disorders. Results: Golgi stressors (brefeldin A [BFA] and monensin) decreased the expression of GM130 and ATP2C1 (two markers of Golgi stress response), induced Golgi apparatus fragmentation, and caused a higher level of oxidative stress and cell apoptosis in mouse myoblast cells. In addition, Golgi stressors upregulated CSE expression and endogenous H2S generation, and exogenously applied H2S was able to protect but inhibition of CSE/H2S system deteriorated Golgi stress response. Activating transcription factor 4 (ATF4) acted as an upstream molecule to increase CSE expression on Golgi stress response. Mechanically, Golgi stressors induced intracellular level of Ca2+, and chelating cellular Ca2+ markedly attenuated Golgi stress response, indicating the key role of Ca2+ in initiating Golgi stress and cell apoptosis. Further, administration of either angiotensin II or BFA initiated Golgi stress response and induced skeletal muscle atrophy in mice, which was further deteriorated by CSE deficiency but rescued by exogenously applied sodium hydrosulfide (NaHS). Innovation and Conclusion: The activation of the CSE/H2S pathway and the decrease of intracellular Ca2+ are two cellular protective mechanisms against Golgi stress, and the CSE/H2S system would be a target for preventing skeletal muscle dysfunctions.This publication has 65 references indexed in Scilit:
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