Isoflurane preconditioning attenuates OGD/R-induced cardiomyocyte cytotoxicity by regulating the miR-210/BNIP3 axis

Dongbo Zhang ¹, Qiaoling Wu ¹, Feifei Liu ¹

⁰Department of Anesthesiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Journal of Applied Toxicology : Jat +

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July 20, 2024

View abstract on PubMed

Summary

Isoflurane preconditioning protects heart cells from injury by upregulating miR-210, a key microRNA. This mechanism involves the miR-210/BNIP3 pathway, highlighting a novel therapeutic target for cardiac protection.

Area Of Science

Cardiology
Molecular Biology
Anesthesiology

Background

Isoflurane, an inhaled anesthetic, exhibits cardioprotective properties.
The underlying molecular mechanisms of isoflurane's cardioprotection remain incompletely understood.
Hypoxia-inducible microRNAs, such as miR-210, play critical roles in cellular stress responses.

Purpose Of The Study

To investigate the role of miR-210 in isoflurane preconditioning-mediated protection against oxygen-glucose deprivation/reperfusion (OGD/R)-induced cardiomyocyte injury.
To elucidate the molecular pathway involving miR-210 and its target BNIP3 in this protective effect.

Main Methods

AC16 human myocardial cells were subjected to OGD/R.
Isoflurane preconditioning was applied.
Cells were transfected with anti-miR-210 or control miRNA to inhibit miR-210 function.
Cell viability, cytotoxicity (LDH, CK-MB), apoptosis, mitochondrial function, and protein expression (Bax, Bcl-2, BNIP3, DRP1, MFN2) were assessed.

Main Results

Isoflurane preconditioning enhanced OGD/R-induced miR-210 upregulation.
Inhibition of miR-210 by anti-miR-210 reversed the protective effects of isoflurane, including reduced cytotoxicity and apoptosis.
Isoflurane preconditioning preserved mitochondrial function and ATP content, effects blunted by anti-miR-210.
The miR-210/BNIP3 axis was identified as a key mediator, with isoflurane regulating BNIP3 expression.

Conclusions

Isoflurane preconditioning confers protection against OGD/R-induced cardiac injury.
This protection is mediated, at least in part, by the upregulation of miR-210.
The miR-210/BNIP3 signaling pathway is crucial for the cardioprotective effects of isoflurane.

Keywords:

cardiomyocyte injury ischemia/reperfusion (I/R) injury isoflurane preconditioning mitochondrial dysfunction