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Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation.

ABSTRACT: Vitamin B6 (VitB6) is a water-soluble vitamin and includes pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. In the current study, we demonstrated that VitB6 could improve lipopolysaccharide (LPS)-induced myocardial injury. We demonstrated that VitB6 can suppress LPS-induced oxidative stress and lipid peroxidation that lead to ferroptosis and apoptosis in vivo and in vitro. Moreover, we found that VitB6 can regulate the expression of iron regulatory proteins, maintaining intracellular iron homeostasis. To confirm that VitB6 could inhibit LPS-induced ferroptosis and apoptosis, we pretreated mice with ferrostatin-1 (Fer-1) and emricasan that efficiently mimicked VitB6 pharmacological effects. This improved the survival rate of mice challenged with a high LPS dose. In addition, VitB6 regulated the expression of LPS-induced apoptosis-related proteins and iron regulatory proteins. It mediated the expression of Nrf2, transcription factor NF-E2-related factor 2, which promoted the expression of antioxidant enzymes and restrained LPS-induced ferroptosis and apoptosis. Overall, our results indicated that VitB6 can be used on novel therapies to relieve LPS-induced myocardial injury.

SUBMITTER: Shan M

PROVIDER: S-EPMC8740299 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation.

Shan Meirong M Yu Xujie X Li Yajie Y Fu Changning C Zhang Cheng C

Frontiers in pharmacology 20211224

Vitamin B6 (VitB6) is a water-soluble vitamin and includes pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. In the current study, we demonstrated that VitB6 could improve lipopolysaccharide (LPS)-induced myocardial injury. We demonstrated that VitB6 can suppress LPS-induced oxidative stress and lipid peroxidation that lead to ferroptosis and apoptosis <i>in vivo</i> and <i>in vitro</i>. Moreover, we found that VitB6 can regulate the expression of iron regulatory proteins, mai ...[more]

PMID: 35002705

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Project description:IntroductionMyocardial ischemia-reperfusion injury (MIRI) is a prevalent complication in patients with myocardial infarction. The pathological mechanism of MIRI remains elusive. Ferroptosis plays a critical role in MIRI. This study aimed to investigate the role of spermidine/spermine N1-acetyltransferase 1 (Sat1) in MIRI by regulation of ferroptosis.MethodsRats and H9C2 cells were used to perform MIRI model. The extent of myocardial damage and associated pathological changes were evaluated. Protein expression was detected by western blot. Then we observed the mitochondrial morphology and measured cell viability and damage. The levels of lipid peroxide and glutathione were measured, and lipid reactive oxygen species (ROS) was quantified. Differentially expressed genes (DEGs) in MIRI were analyzed. Moreover, to explore the role of Sat1 in MIRI, this study utilized adeno-associated virus 9 and lentiviral transduction to modulate Sat1 expression in rats and H9C2 cells, respectively. The transcription factor that regulates Sat1 expression was predicated. Luciferase reporter gene experiment was conducted to reveal the potential sites of Sox2 binding to Sat1.ResultsThis study revealed that ferroptosis was involved in MIRI. Through bioinformatic analysis, Sat1 was identified as a significant gene in MIRI, which has been reported as an inducer of ferroptosis. Our results showed that Sat1 expression was significantly increased in MIRI. Next, the study showed that inhibition of Sat1 alleviated MIRI by suppressing ferroptosis in vivo and in vitro, and over-expression of Sat1 promoted MIRI via activation of ferroptosis. Furthermore, Sat1 and its interacting genes were enriched in several signaling pathways, including ferroptosis and the MAPK signaling pathway. The results showed that Sat1 regulated MIRI through ferroptosis via MAPK/ERK pathway. Moreover, it is found that Sox2 can suppress Sat1 expression at the transcriptional level. The potential binding site was TAACAAAGGAA.ConclusionIn sum, this study demonstrated Sat1 expression was increased in MIRI, inhibition of Sat1 can alleviate MIRI by regulating ferroptosis via MAPK/ERK pathway, and Sat1 was negatively regulated by Sox2. These findings suggested that Sat1 may serve as a potential therapeutic target for the treatment of MIRI.

Dataset Information

Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation.

Publications

Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation.

Similar Datasets

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