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RXR agonists inhibit oxidative stress-induced apoptosis in H9c2 rat ventricular cells
Peiren Shan1, Jun Pu, Ancai Yuan
1Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, China.
Abstract:
Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. We examined its role in regulating oxidative stress-induced apoptosis in H9c2 rat ventricular cells. We showed for the first time that functional RXR protein was downregulated by hydrogen peroxide (H2O2) in H9c2 cardiomyocytes. Natural and synthetic agonists of RXR, 9-cis-RA, and LGD1069 respectively, prevented H2O2-triggered apoptosis, and this anti-apoptotic effect was inhibited by the RXR antagonist HX531. Further investigation into the protective mechanisms of RXR demonstrated that H2O2-induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and caspase-3 activation were all significantly attenuated by pretreatment with RXR agonists. Furthermore, this protection was associated with a reduction in intracellular reactive oxygen species and an upregulation in catalase activity. Thus, these data indicate that pharmacological activation of RXR exerts protective effects against H2O2-induced apoptosis in H9c2 rat ventricular cells through antioxidant and mitochondria-protective mechanisms.
Insights
Pharmacological activation of Retinoid X receptor (RXR) protects against hydrogen peroxide-induced apoptosis in heart cells. RXR agonists reduce oxidative stress and protect mitochondria, offering a potential therapeutic strategy.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Retinoid X receptor (RXR) is crucial for intracellular signaling pathways.
- Oxidative stress contributes to cardiac cell apoptosis.
Purpose of the Study:
- To investigate the role of RXR in regulating oxidative stress-induced apoptosis in H9c2 rat ventricular cells.
- To explore the protective mechanisms of RXR activation against hydrogen peroxide (H2O2)-induced cell damage.
Main Methods:
- Utilized H9c2 rat ventricular cells exposed to H2O2.
- Administered RXR agonists (9-cis-RA, LGD1069) and an antagonist (HX531).
- Assessed apoptosis, mitochondrial membrane potential, cytochrome c release, caspase-3 activation, reactive oxygen species (ROS) levels, and catalase activity.
Main Results:
- Functional RXR protein was downregulated by H2O2 in H9c2 cardiomyocytes.
- RXR agonists prevented H2O2-induced apoptosis, an effect blocked by the RXR antagonist.
- RXR activation attenuated mitochondrial dysfunction, reduced ROS, and increased catalase activity.
Conclusions:
- Pharmacological activation of RXR provides significant protection against H2O2-induced apoptosis in H9c2 cells.
- RXR exerts protective effects via antioxidant mechanisms and by preserving mitochondrial integrity.
