Preprint Article Version 1 This version is not peer-reviewed

The ABA/LANCL1-2 Hormone Receptors System Controls ROS Production in Cardiomyocytes through ERRα

Version 1 : Received: 18 July 2024 / Approved: 18 July 2024 / Online: 19 July 2024 (11:01:47 CEST)

How to cite: Spinelli, S.; Guida, L.; Passalacqua, M.; Magnone, M.; Caushi, B.; Zocchi, E.; Sturla, L. The ABA/LANCL1-2 Hormone Receptors System Controls ROS Production in Cardiomyocytes through ERRα. Preprints 2024, 2024071570. https://doi.org/10.20944/preprints202407.1570.v1 Spinelli, S.; Guida, L.; Passalacqua, M.; Magnone, M.; Caushi, B.; Zocchi, E.; Sturla, L. The ABA/LANCL1-2 Hormone Receptors System Controls ROS Production in Cardiomyocytes through ERRα. Preprints 2024, 2024071570. https://doi.org/10.20944/preprints202407.1570.v1

Abstract

Rat H9c2 cardiomyocytes overexpressing the abscisic acid (ABA) hormone receptors LANCL1 and LANCL2 have an increased mitochondrial proton gradient, respiration and vitality after hypoxia/reoxygenation. Our aim was to investigate the role of the ABA/LANCL1-2 system in ROS turnover in H9c2. H9c2 cells were retrovirally infected to induce overexpression or silencing of LANCL1 and LANCL2, without or with the concomitant silencing of the transcription factor ERRα. Enzymes involved in radical production or scavenging were studied by qPCR and Western blot. Mitochondrial proton gradient and ROS were measured with specific fluorescent probes. ROS generating enzymes decreased, ROS-scavenging enzymes increased, and mitochondrial ROS were reduced in LANCL1/2-overexpressing vs. control cells infected with the empty vector, while the opposite occurred in LANCL1/2-silenced cells. Knock-down of ERRα abrogated all beneficial effects on ROS turnover in LANCL1/2 overexpressing cells. Taken together, these results indicate that the ABA/LANCL1-2 system controls ROS turnover in H9c2 via ERRα. The ABA/LANCL system emerges as a promising target to improve cardiomyocyte mitochondrial function and resilience to oxidative stress.

Keywords

ROS-producing enzymes; ROS-scavenging enzymes; mitochondrial proton gradient; COX2; XO; NOX4; SOD2; GPX4; ERRα

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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