DJ-1 plays an obligatory role in the cardioprotection of delayed hypoxic preconditioning against hypoxia/reoxygenation-induced oxidative stress through maintaining mitochondrial complex I activity.

DJ-1 was recently reported to mediate the cardioprotection of delayed hypoxic preconditioning (DHP) by suppressing hypoxia/reoxygenation (H/R)-induced oxidative stress, but its mechanism against H/R-induced oxidative stress during DHP is not fully elucidated. Here, using the well-established cellular model of DHP, we again found that DHP significantly improved cell viability and reduced lactate dehydrogenase release with concurrently up-regulated DJ-1 protein expression in H9c2 cells subjected to H/R. Importantly, DHP efficiently improved mitochondrial complex I activity following H/R and attenuated H/R-induced mitochondrial reactive oxygen species (ROS) generation and subsequent oxidative stress, as demonstrated by a much smaller decrease in reduced glutathione/oxidized glutathione ratio and a much smaller increase in intracellular ROS and malondialdehyde contents than that observed for the H/R group.

DJ-1 preserving mitochondrial complex I activity plays a critical role in resveratrol-mediated cardioprotection against hypoxia/reoxygenation-induced oxidative stress.

Resveratrol has been demonstrated to have cardioprotective effects by attenuating ischemia/reperfusion (I/R)-induced oxidative stress injury, but its in-depth molecular mechanisms against I/R-induced oxidative stress is not fully elaborated. DJ-1 plays a role in maintenance of mitochondrial complex I activity and is closely associated with oxidative stress. Therefore, this study sought to determine the contribution of DJ-1-mediated maintenance of mitochondrial complex I activity to the anti-oxidative stress effect of Resveratrol in the H9c2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R).

Sasanquasaponin induces increase of Cl‑/HCO3‑ exchange of anion exchanger 3 and promotes intracellular Cl‑ efflux in hypoxia/reoxygenation cardiomyocytes.

Anion exchanger 3 (AE3) is known to serve crucial roles in maintaining intracellular chloride homeostasis by facilitating the reversible electroneutral exchange of Cl‑ for HCO3‑ across the plasma membrane. Our previous studies reported that sasanquasaponin (SQS) can inhibit hypoxia/reoxygenation (H/R)‑induced elevation of intracellular Cl‑ concentration ([Cl‑]i) and elicit cardioprotection by favoring Cl‑/HCO3‑ exchange of AE3. However, the molecular basis for SQS‑induced increase of Cl‑/HCO3‑ exchange of AE3 remains unclear.

Extracellular Cl-free-induced cardioprotection against hypoxia/reoxygenation is associated with attenuation of mitochondrial permeability transition pore.

The isotonic substitution of extracellular chloride by gluconate (extracellular Cl-free) has been demonstrated to elicit cardioprotection by attenuating ischaemia/reperfusion-induced elevation of intracellular chloride ion concentration ([Cl]). However, the downstream mechanism underlying the cardioprotective effect of extracellular Cl-free is not fully established. Here, it was investigated whether extracellular Cl-free attenuates mitochondrial dysfunction after hypoxia/reoxygenation (H/R) and whether mitochondrial permeability transition pore (mPTP) plays a key role in the extracellular Cl-free cardioprotection.

Sasanquasaponin-induced cardioprotection involves inhibition of mPTP opening via attenuating intracellular chloride accumulation.

Sasanquasaponin (SQS) has been reported to elicit cardioprotection by suppressing hypoxia/reoxygenation (H/R)-induced elevation of intracellular chloride ion concentration ([Cl]). Given that the increased [Cl] is involved to modulate the mitochondrial permeability transition pore (mPTP), we herein sought to further investigate the role of mPTP in the cardioprotective effect of SQS on H/R injury. H9c2 cells were incubated for 24h with or without 10μM SQS followed by H/R.