Paraoxonase 2 protects against acute myocardial ischemia-reperfusion injury by modulating mitochondrial function and oxidative stress via the PI3K/Akt/GSK-3β RISK pathway

Journal of Molecular and Cellular Cardiology
Dawoud SulaimanSrinivasa T Reddy

Abstract

To investigate the novel role of Paraoxonase 2 (PON2) in modulating acute myocardial ischemia-reperfusion injury (IRI). IRI was induced both in vivo and ex vivo in male, C57BL6/J (WT) and PON2-deficient (PON-def) mice. In addition, in vitro hypoxia-reoxygenation injury (HRI) was induced in H9c2 cells expressing empty vector (H9c2-EV) or human PON2 (H9c2-hPON2) ± LY294002 (a potent PI3K inhibitor). Infarct size, PON2 gene expression, mitochondrial calcium retention capacity (CRC), reactive oxygen species (ROS) generation, mitochondrial membrane potential, CHOP and pGSK-3β protein levels, and cell apoptosis were evaluated. PON2 gene expression is upregulated in WT mice following in vivo IRI. PON2-def mice exhibit a 2-fold larger infarct, increased CHOP levels, and reduced pGSK-3β levels compared to WT controls. Global cardiac mitochondria isolated from PON2-def mice exhibit reduced CRC and increased ROS production. Cardiomyocytes isolated from PON2-def mice subjected to ex vivo IRI have mitochondria with reduced CRC (also seen under non-IRI conditions), and increased ROS generation and apoptosis compared to WT controls. PON2 knockdown in H9c2 cells subjected to HRI leads to an increase in mitochondrial membrane depolarization. H9...Continue Reading

Citations

May 6, 2019·Antioxidants·Débora LevySérgio Paulo Bydlowski
Jun 5, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Yanbo ChenLianqun Cui
Jan 20, 2020·Journal of Cellular and Molecular Medicine·Lin CongMingyuan Huang
Dec 31, 2020·Antioxidants·Cadiele Oliana ReichertSergio P Bydlowski
Dec 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ajda Taler-VerčičAljoša Bavec
Feb 11, 2021·Antioxidants·Giuseppe MancoTeresa Maria Carusone
Apr 7, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hewang LeePedro A Jose
Jun 1, 2021·Oxidative Medicine and Cellular Longevity·Mi XiangXiangning Cui
Jul 4, 2021·Neurotoxicology and Teratology·Jacqueline M GarrickLucio G Costa

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