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11-07-2022 | Septicemia | Original Research Article

Heme oxygenase-1 protects against endotoxin-induced acute lung injury depends on NAD⁺-mediated mitonuclear communication through PGC1α/PPARγ signaling pathway

Authors: Simeng He, Jia Shi, Wenming Liu, Shihan Du, Yuan Zhang, Lirong Gong, Shuan Dong, Xiangyun Li, Qiaoying Gao, Jing Yang, Jianbo Yu

Published in: Inflammation Research | Issue 9/2022

Abstract

Endotoxin-induced acute lung injury (ALI) is a challenging life-threatening disease for which no specific therapy exists. Mitochondrial dysfunction is corroborated as hallmarks in sepsis which commonly disrupt mitochondria-centered cellular communication networks, especially mitonuclear crosstalk, where the ubiquitous cofactor nicotinamide adenine dinucleotide (NAD⁺) is essential for mitonuclear communication. Heme oxygenase-1 (HO-1) is critical for maintaining mitochondrial dynamic equilibrium and regulating endoplasmic reticulum (ER) and Golgi stress to alleviating acute lung injury. However, it is unclear whether HO-1 regulates NAD⁺-mediated mitonuclear communication to exert the endogenous protection during endotoxin-induced ALI. In this study, we observed HO-1 attenuated endotoxin-induced ALI by regulated NAD⁺ levels and NAD⁺ affected the mitonuclear communication, including mitonuclear protein imbalance and UPR^mt to alleviate lung damage. We also found the protective effect of HO-1 depended on NAD⁺ and NAD⁺-mediated mitonuclear communication. Furtherly, the inhibition of the PGC1α/PPARγ signaling exacerbates the septic lung injury by reducing NAD⁺ levels and repressing the mitonuclear protein imbalance and UPR^mt. Altogether, our study certified that HO-1 ameliorated endotoxin-induced acute lung injury by regulating NAD⁺ and NAD⁺-mediated mitonuclear communications through PGC1α/PPARγ pathway. The present study provided complementary evidence for the cytoprotective effect of HO-1 as a potential target for preventing and attenuating of endotoxin-induced ALI.

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Title: Heme oxygenase-1 protects against endotoxin-induced acute lung injury depends on NAD+-mediated mitonuclear communication through PGC1α/PPARγ signaling pathway
Authors: Simeng He
Jia Shi
Wenming Liu
Shihan Du
Yuan Zhang
Lirong Gong
Shuan Dong
Xiangyun Li
Qiaoying Gao
Jing Yang
Jianbo Yu
Publication date: 11-07-2022
Publisher: Springer International Publishing
Keywords: Septicemia
Septicemia
Acute Respiratory Distress-Syndrome
Published in: Inflammation Research / Issue 9/2022
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-022-01605-y

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