Katoch S, Patial V. Sirtuin 1 in regulating the p53/glutathione peroxidase 4/gasdermin D axis in acute liver failure. World J Gastroenterol 2024; 30(34): 3850-3855 [DOI: 10.3748/wjg.v30.i34.3850]
Corresponding Author of This Article
Vikram Patial, PhD, Principal Scientist, Associate Professor, Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Post Box No. 6, Palampur 176061, Himachal Pradesh, India. vikrampatial@ihbt.res.in
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Sep 14, 2024; 30(34): 3850-3855 Published online Sep 14, 2024. doi: 10.3748/wjg.v30.i34.3850
Sirtuin 1 in regulating the p53/glutathione peroxidase 4/gasdermin D axis in acute liver failure
Swati Katoch, Vikram Patial
Swati Katoch, Vikram Patial, Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India
Swati Katoch, Vikram Patial, Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India
Author contributions: Katoch S collected the literature and wrote the manuscript; Patial V contributed to designing, manuscript writing and editing; Both authors have read and approved the final manuscript.
Supported byCSIR, India, No. MLP0204.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Vikram Patial, PhD, Principal Scientist, Associate Professor, Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Post Box No. 6, Palampur 176061, Himachal Pradesh, India. vikrampatial@ihbt.res.in
Received: March 15, 2024 Revised: August 14, 2024 Accepted: August 21, 2024 Published online: September 14, 2024 Processing time: 178 Days and 20 Hours
Abstract
In this editorial, we comment on the article by Zhou et al. The study reveals the connection between ferroptosis and pyroptosis and the effect of silent information regulator sirtuin 1 (SIRT1) activation in acute liver failure (ALF). ALF is characterized by a sudden and severe liver injury resulting in significant hepatocyte damage, often posing a high risk of mortality. The predominant form of hepatic cell death in ALF involves apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis. Glutathione peroxidase 4 (GPX4) inhibition sensitizes the cell to ferroptosis and triggers cell death, while Gasdermin D (GSDMD) is a mediator of pyroptosis. The study showed that ferroptosis and pyroptosis in ALF are regulated by blocking the p53/GPX4/GSDMD pathway, bridging the gap between the two processes. The inhibition of p53 elevates the levels of GPX4, reducing the levels of inflammatory and liver injury markers, ferroptotic events, and GSDMD-N protein levels. Reduced p53 expression and increased GPX4 on deletion of GSDMD indicated ferroptosis and pyroptosis interaction. SIRT1 is a NAD-dependent deacetylase, and its activation attenuates liver injury and inflammation, accompanied by reduced ferroptosis and pyroptosis-related proteins in ALF. SIRT1 activation also inhibits the p53/GPX4/GSDMD axis by inducing p53 acetylation, attenuating LPS/D-GalN-induced ALF.
Core Tip: Ferroptosis and pyroptosis are crucial modes of hepatic cell death in acute liver failure (ALF), and their close association leads to the sudden progression of liver failure. Silent information regulator sirtuin 1 inhibits p53 activity by deacetylation, thereby promoting cell survival. Inhibition of p53 activity affects downstream regulators like Glutathione peroxidase 4 (GPX4) and Gasdermin D (GSDMD). The overexpression of GPX4 and reduced levels of GSDMD protect the cell from pyroptosis and ferroptosis, indicating the close link between these mechanisms in ALF.
