PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis.

Cell death Ferroptosis Mechanism Myocardial I/R injury PIM3

Journal

Genes & genomics
ISSN: 2092-9293
Titre abrégé: Genes Genomics
Pays: Korea (South)
ID NLM: 101481027

Informations de publication

Date de publication:
26 Dec 2023
Historique:
received: 28 12 2022
accepted: 22 06 2023
revised: 16 06 2023
medline: 27 12 2023
pubmed: 27 12 2023
entrez: 26 12 2023
Statut: aheadofprint

Résumé

Myocardial ischemia/reperfusion (I/R) injury is closely related with cardiovascular diseases; however, the underlying pathogenic mechanisms remain not fully understood. This study sought to investigate the effect and mechanisms of PIM3 implicated in myocardial I/R injury using a rat model of myocardial I/R injury and a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) induction. The morphology changes were detected by HE staining while cell viability was accessed by the CCK-8 method. The characteristics of ferroptosis were evaluated by ROS production, MDA content, SOD level, iron content, TfR1, FTH1, and GPX4 expression. Myocardial I/R operation increased myocardial tissue damage in rats, while OGD/R treatment reduced the viability of H9c2 cells. Both myocardial I/R operation and OGD/R stimulation increased ferroptosis, as demonstrated by elevated ROS, MDA, iron content, decreased SOD level, upregulation of TfR1, and downregulation of FTH1 and GPX4. Additionally, myocardial I/R modeling or OGD/R treatment enhanced the expression of PIM3. Silencing of PIM3 inhibited ferroptosis, which resulted in alleviated myocardial I/R-induced damage and improved H9c2 cell survival. Our findings highlight a vital role of PIM3 in myocardial I/R injury, indicating that PIM3-targeting ferroptosis may be a promising target for the development of novel therapies of myocardial I/R injury-associated diseases.

Sections du résumé

BACKGROUND BACKGROUND
Myocardial ischemia/reperfusion (I/R) injury is closely related with cardiovascular diseases; however, the underlying pathogenic mechanisms remain not fully understood. This study sought to investigate the effect and mechanisms of PIM3 implicated in myocardial I/R injury using a rat model of myocardial I/R injury and a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) induction.
METHODS METHODS
The morphology changes were detected by HE staining while cell viability was accessed by the CCK-8 method. The characteristics of ferroptosis were evaluated by ROS production, MDA content, SOD level, iron content, TfR1, FTH1, and GPX4 expression.
RESULTS RESULTS
Myocardial I/R operation increased myocardial tissue damage in rats, while OGD/R treatment reduced the viability of H9c2 cells. Both myocardial I/R operation and OGD/R stimulation increased ferroptosis, as demonstrated by elevated ROS, MDA, iron content, decreased SOD level, upregulation of TfR1, and downregulation of FTH1 and GPX4. Additionally, myocardial I/R modeling or OGD/R treatment enhanced the expression of PIM3. Silencing of PIM3 inhibited ferroptosis, which resulted in alleviated myocardial I/R-induced damage and improved H9c2 cell survival.
CONCLUSIONS CONCLUSIONS
Our findings highlight a vital role of PIM3 in myocardial I/R injury, indicating that PIM3-targeting ferroptosis may be a promising target for the development of novel therapies of myocardial I/R injury-associated diseases.

Identifiants

DOI: 10.1007/s13258-023-01475-6 PMID: 38148455
pubmed: 38148455
doi: 10.1007/s13258-023-01475-6
pii: 10.1007/s13258-023-01475-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.

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Auteurs

Ting Li (T)

Department of Cardiovascular Medicine, The First Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Fangyao Liu (F)

Department of Cardiovascular Medicine, The Second Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Ying Tan (Y)

Department of Cardiovascular Medicine, The First Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Yutao Peng (Y)

Department of Cardiovascular Medicine, The First Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Xuefeng Xu (X)

Department of Cardiovascular Medicine, The First Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Yushan Yang (Y)

School of Resource, Environment and Safety Engineering, Univerity of South China, Hengyang, 421001, Hunan, People's Republic of China. 632700597@qq.com.

Classifications MeSH