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

Panagaki, Theodora; Randi, Elisa B.; Szabo, Csaba

doi:10.3390/biom10121692

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

Theodora Panagaki

Elisa B. Randi

and

Csaba Szabo

Chair of Pharmacology, Section of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland

Authors to whom correspondence should be addressed.

Biomolecules 2020, 10(12), 1692; https://doi.org/10.3390/biom10121692

Received: 13 November 2020 / Revised: 12 December 2020 / Accepted: 14 December 2020 / Published: 18 December 2020

(This article belongs to the Special Issue 2020 Feature Papers by Biomolecules’ Editorial Board Members)

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Abstract

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. View Full-Text

Keywords: hydrogen sulfide; ER stress; mitochondria; autophagy; hepatic UPR

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Panagaki, T.; Randi, E.B.; Szabo, C. Role of Hydrogen Sulfide and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of the Endoplasmic Reticulum Stress Response in Hepatocytes. Biomolecules 2020, 10, 1692. https://doi.org/10.3390/biom10121692

AMA Style

Panagaki T, Randi EB, Szabo C. Role of Hydrogen Sulfide and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of the Endoplasmic Reticulum Stress Response in Hepatocytes. Biomolecules. 2020; 10(12):1692. https://doi.org/10.3390/biom10121692

Chicago/Turabian Style

Panagaki, Theodora, Elisa B. Randi, and Csaba Szabo. 2020. "Role of Hydrogen Sulfide and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of the Endoplasmic Reticulum Stress Response in Hepatocytes" Biomolecules 10, no. 12: 1692. https://doi.org/10.3390/biom10121692

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

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