Related Experiment Video
Updated: Aug 10, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
PGAM5 expression levels in heart failure and protection ROS-induced oxidative stress and ferroptosis by Keap1/Nrf2
Shuangfei Li1, Ping Wen1, Dayong Zhang1
1Department of Cardiovascular Medicine, Sichuan Mianyang 404 Hospital, Mianyang, China.
Objectives:
As a common and frequently occurring disease, heart failure has been paid more and more attention, but the mechanism of its occurrence and development is still unclear. This study investigated that PGAM5 expression levels in heart failure and its underlying mechanisms in vivo and in vitro.
Methods:
The inhibition of PGAM5 mRNA expression levels in patients with heart failure was compared with the normal group.
Results:
The serum of PGAM5 mRNA expression was negative correlation with collagen I and collagen III in patients with heart failure. PGAM5 mRNA and protein expression in the heart tissue of mice with heart failure were down-regulated at a time-dependent rate. The inhibition of PGAM5 presented heart failure in the model. PGAM5 reduced inflammation and inhibited ROS-induced oxidative stress in models of heart failure. PGAM5 reduced Ferroptosis in models of heart failure. PGAM5 regulated Keap1/Nrf2 signaling pathway. IP also showed that PGAM5 protein combined with the Keap1 protein. PGAM5 could increase Keap1 protein ubiquitination. Keap1 inhibition affected the effects of PGAM5 in model of heart failure.
Conclusions:
We conclude that the protection of PGAM5 reduced ROS-induced oxidative stress and ferroptosis by the Keap1/Nrf2 signaling pathway in heart failure, suggesting that targeting this mechanism of PGAM5 may be a feasible strategy to treat heart failure.
Insights
PGAM5 (protein گیمো গ্লাইকোসিলেশন ম্যাপিং 5) expression is reduced in heart failure. Restoring PGAM5 protects against oxidative stress and ferroptosis via the Keap1/Nrf2 pathway, offering a potential heart failure treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Disease
Background:
- Heart failure is a prevalent condition with incompletely understood pathogenesis.
- Investigating novel molecular players like PGAM5 is crucial for understanding heart failure development.
Purpose of the Study:
- To investigate the expression levels of PGAM5 in heart failure.
- To elucidate the underlying mechanisms of PGAM5 in heart failure pathogenesis in vivo and in vitro.
Main Methods:
- Compared PGAM5 mRNA expression in heart failure patients versus healthy controls.
- Assessed PGAM5 mRNA and protein levels in mouse models of heart failure.
- Examined the effects of PGAM5 inhibition and its interaction with the Keap1/Nrf2 signaling pathway.
Main Results:
- PGAM5 mRNA expression was downregulated in heart failure patients and mice.
- PGAM5 inhibition exacerbated heart failure phenotypes.
- PGAM5 demonstrated protective effects by reducing inflammation, ROS-induced oxidative stress, and ferroptosis.
- PGAM5 interacts with Keap1, promoting its ubiquitination and regulating the Keap1/Nrf2 pathway.
Conclusions:
- PGAM5 protects against heart failure by mitigating oxidative stress and ferroptosis through the Keap1/Nrf2 signaling pathway.
- Targeting the PGAM5-Keap1/Nrf2 axis represents a promising therapeutic strategy for heart failure.
More Related Videos
04:01Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
07:40Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
