Dataset Information

Sirtuin 5-mediated desuccinylation of ALDH2 alleviates mitochondrial oxidative stress following acetaminophen-induced acute liver injury

ABSTRACT: WT mice and SIRT5 knockout mice were injected with APAP by intraperitoneal injection, and liver tissue specimens were taken 24 hours later for protein succinylation modification histology analysis

ORGANISM(S): Mus Musculus

SUBMITTER: Sanyang Chen

PROVIDER: PXD050121 | iProX | Sat Feb 24 00:00:00 GMT 2024

REPOSITORIES: iProX

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Publications

Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.

Yu Qiwen Q Zhang Jiakai J Li Jiye J Song Yaodong Y Pan Jie J Mei Chaopeng C Cui Mengwei M He Qianqian Q Wang Haifeng H Li Huihui H Cheng Bo B Zhang Yan Y Guo Wenzhi W Zhu Changju C Chen Sanyang S

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240819 39

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP-induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, b ...[more]

PMID: 39159058

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Project description:Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections. Experiment Overall Design: In this study, adult and aged mice were injected intraperitoneal with sterile saline or Escherichia coli LPS (0.33 mg/kg, ~10 µg/mouse; serotype 0127:B8, Sigma). This dosage of LPS was used because it induces a mild transient sickness behavior in young adults. Mice were killed 4 h after saline or LPS injection by CO2 asphyxiation. Blood samples were collected and brains were removed, separated in half at the longitudinal fissure, frozen in liquid nitrogen, and stored (-80°C) until assaying. Total RNA was later isolated from some brain samples for microarray analysis (n=3).

Dataset Information

Sirtuin 5-mediated desuccinylation of ALDH2 alleviates mitochondrial oxidative stress following acetaminophen-induced acute liver injury

Publications

Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.

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