Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress

AbstractRolipram specifically inhibits phosphodiesterase (PDE) 4, thereby preventing inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to play a neuroprotective role in some central nervous system (CNS) diseases. However, the role of PDE4 and the potential protective effect of rolipram on the pathophysiological process of intracerebral haemorrhage (ICH) are still not entirely clear. In this study, a mouse model of ICH was established by the collagenase method. Rolipram reduced brain oedema, blood–brain barrier (BBB) leakage, neuronal apoptosis and inflammatory cytokine release and improved neurological function in our mouse model of ICH. Moreover, rolipram increased the levels of cAMP and silent information regulator 1 (SIRT1) and upregulated the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, these effects of rolipram could be reversed by the SIRT1 inhibitor sirtinol. In conclusion, rolipram can play a neuroprotective role in the pathological process of ICH by activating the cAMP/AMPK/SIRT1 pathway.

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Role of Hydrogen Sulfide and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of the Endoplasmic Reticulum Stress Response in Hepatocytes

Biomolecules ◽

10.3390/biom10121692 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1692

Author(s):

Theodora Panagaki ◽

Elisa B. Randi ◽

Csaba Szabo

Keyword(s):

Endoplasmic Reticulum ◽

Hydrogen Sulfide ◽

Liver Disease ◽

Er Stress ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Endoplasmic Reticulum Stress Response ◽

Functional Responses ◽

Mercaptopyruvate Sulfurtransferase

It is estimated that over 1.5 billion people suffer from various forms of chronic liver disease worldwide. The emerging prevalence of metabolic syndromes and alcohol misuse, along with the lack of disease-modifying agents for the therapy of many severe liver conditions predicts that chronic liver disease will continue to be a major problem in the future. Better understanding of the underlying pathogenetic mechanisms and identification of potential therapeutic targets remains a priority. Herein, we explored the potential role of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide (H2S) system in the regulation of the endoplasmic reticulum (ER) stress and of its downstream processes in the immortalized hepatic cell line HepG2 in vitro. ER stress suppressed endogenous H2S levels and pharmacological supplementation of H2S with sodium hydrogen sulfide (NaHS) mitigated many aspects of ER stress, culminating in improved cellular bioenergetics and prevention of autophagic arrest, thereby switching cells’ fate towards survival. Genetic silencing of 3-MST or pharmacological inhibition of the key enzymes involved in hepatocyte H2S biosynthesis exacerbated many readouts related to ER-stress or its downstream functional responses. Our findings implicate the 3-MST/H2S system in the intracellular network that governs proteostasis and ER-stress adaptability in hepatocytes and reinforce the therapeutic potential of pharmacological H2S supplementation.

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Persulfidation of ATG18a regulates autophagy under ER stress in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2023604118 ◽

2021 ◽

Vol 118 (20) ◽

pp. e2023604118

Author(s):

Angeles Aroca ◽

Inmaculada Yruela ◽

Cecilia Gotor ◽

Diane C. Bassham

Keyword(s):

Endoplasmic Reticulum ◽

Hydrogen Sulfide ◽

Er Stress ◽

Molecular Mechanism ◽

Stress Responses ◽

Binding Capacity ◽

Plant Cells ◽

Binding Activity ◽

Negative Regulator

Hydrogen sulfide (H2S) is an endogenously generated gaseous signaling molecule, which recently has been implicated in autophagy regulation in both plants and mammals through persulfidation of specific targets. Persulfidation has been suggested as the molecular mechanism through which sulfide regulates autophagy in plant cells. ATG18a is a core autophagy component that is required for bulk autophagy and also for reticulophagy during endoplasmic reticulum (ER) stress. In this research, we revealed the role of sulfide in plant ER stress responses as a negative regulator of autophagy. We demonstrate that sulfide regulates ATG18a phospholipid-binding activity by reversible persulfidation at Cys103, and that this modification activates ATG18a binding capacity to specific phospholipids in a reversible manner. Our findings strongly suggest that persulfidation of ATG18a at C103 regulates autophagy under ER stress, and that the impairment of persulfidation affects both the number and size of autophagosomes.

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Involvement of MicroRNA-133a in the Protective Effect of Hydrogen Sulfide against Ischemia/Reperfusion-Induced Endoplasmic Reticulum Stress and Cardiomyocyte Apoptosis

Pharmacology ◽

10.1159/000492969 ◽

2018 ◽

Vol 103 (1-2) ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Lin Ren ◽

Qian Wang ◽

Yu Chen ◽

Yanzhuo Ma ◽

Dongmei Wang

Keyword(s):

Hydrogen Sulfide ◽

Protective Effect ◽

Er Stress ◽

Heart Diseases ◽

Ischemia Reperfusion ◽

Annexin V ◽

Cardiomyocyte Apoptosis ◽

Migration And Invasion

Aim: Myocardial ischemia/reperfusion (I/R) injury is a severe trauma that cells undergo and is associated with cardiomyocyte apoptosis. Recently, miRNAs have been demonstrated to play an important role in cardiovascular biology and disease. However, whether the miR-133a and ER stress play a role in hydrogen sulfide (H2S) protection of cardiomyocytes against I/R-induced apoptosis remains unclear. Methods: The neonatal cardiomyocytes were prepared to be treated with H2S or transfected with miR-133a activator or miR-133a inhibitor, either separately or in combination. Non-treated cardiomyocytes served as control. The ER stress biomarker GRP78, CHOP, and eIF2α expression levels were measured by Western blot. Cell apoptosis was assessed by flow cytometry after staining with the Annexin V- FITC. Proliferation was monitored by BrdU labeling, while cell migration and invasion were determined by Transwell assays. Results: Pre-treatment of H2S and overexpression of miR-133a reversed I/R-induced ER stress and cardiomyocyte apoptosis in vitro and in vivo. The proliferation, migration, and invasion of cardiomyocytes were significantly increased by co-treatment with H2S and overexpression of miR-133a. Conclusion: These findings suggest the protective effect of miR-133a against I/R-induced ER stress and cardiomyocyte apoptosis and its enhancement of cell motility. Thus, cardioprotection by miR-133a overexpression provides a novel therapeutic approach to the treatment of ischemic heart diseases.

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Role of Calcium Channels in the Protective Effect of Hydrogen Sulfide in Rat Cardiomyoblasts

Cellular Physiology and Biochemistry ◽

10.1159/000358690 ◽

2014 ◽

Vol 33 (4) ◽

pp. 1205-1214 ◽

Cited By ~ 19

Author(s):

Daniele Avanzato ◽

Annalisa Merlino ◽

Sabina Porrera ◽

Rui Wang ◽

Luca Munaron ◽

...

Keyword(s):

Hydrogen Sulfide ◽

Calcium Channels ◽

Protective Effect

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The ER stress-autophagy axis: implications for cognitive dysfunction in diabetes mellitus

Clinical Science ◽

10.1042/cs20200235 ◽

2020 ◽

Vol 134 (11) ◽

pp. 1255-1258

Author(s):

Qingzhang Zhu

Keyword(s):

Er Stress ◽

Cognitive Dysfunction ◽

Hydrogen sulfide protects SH-SY5Y cells against 6-hydroxydopamine-induced endoplasmic reticulum stress

AJP Cell Physiology ◽

10.1152/ajpcell.00281.2011 ◽

2012 ◽

Vol 303 (1) ◽

pp. C81-C91 ◽

Cited By ~ 38

Author(s):

Li Xie ◽

Chi Xin Tiong ◽

Jin-Song Bian

Keyword(s):

Endoplasmic Reticulum ◽

Hydrogen Sulfide ◽

Protective Effect ◽

Er Stress ◽

Stress Responses ◽

Initiation Factor ◽

Akt Inhibitor ◽

Stress Injury ◽

Sodium Hydrosulfide ◽

6 Hydroxydopamine

Endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative diseases, including Parkinson's disease. The present study attempted to investigate the effect of hydrogen sulfide (H2S) on 6-hydroxydopamine (6-OHDA)-induced ER stress in SH-SY5Y cells. We found in the present study that exogenous application of sodium hydrosulfide (NaHS; an H2S donor, 100 μM) significantly attenuated 6-OHDA (50 μM)-induced cell death. NaHS also reversed the upregulation of cleaved poly(ADP-ribose) polymerase and caspase 9 in 6-OHDA-treated cells. Consistent with its cytoprotective effects, NaHS markedly reduced 6-OHDA induced-ER stress responses, including the upregulated levels of eukaryotic initiation factor-2α phosphorylation, glucose-regulated protein 78, and C/EBP homologous protein expression. The protective effect of H2S on ER stress was attenuated by blockade of Akt activity with an Akt inhibitor or inhibition of heat shock protein (Hsp)90 with geldanamycin but not by suppression of ERK1/2 with PD-98059. Blockade of Akt also significantly decreased the protein abundance of Hsp90 in SH-SY5Y cells. Moreover, overexpression of cystathionine β-synthase (a main H2S-synthesizing enzyme in the brain) elevated the Hsp90 protein level and suppressed 6-OHDA-induced ER stress. In conclusion, the protective effect of H2S against 6-OHDA-induced ER stress injury in SH-SY5Y cells involves the Akt-Hsp90 pathway.

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