Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: the critical role of Coenzyme Q9/10

Abstract

AbstractImpaired mitochondrial function concomitant to enhanced oxidative stress-induced damage are well established mechanisms involved in hyperlipidemia-induced cardiotoxicity. Coenzyme Q9/10 (CoQ) is known to be a critical component of the mitochondrial electron transport chain that efficiently supports the process of bioenergetics in addition to its antioxidant activities. However, there is very limited information on the direct effect of myocardial lipid overload on endogenous CoQ levels in association with mitochondrial respiration and oxidative stress status. Here, such effects were explored by exposing H9c2 cardiomyocytes to various doses (0.15 to 1 mM) of palmitate for 24 hours. The results demonstrated that palmitate doses ≥ 0.25 mM are enough to impair mitochondrial respiration and cause oxidative stress. Although endogenous CoQ levels are enhanced by palmitate doses ≤ 5 mM, this is not enough to counteract oxidative stress, but is sufficient to maintain cell viability of cardiomyocytes, suggesting a compensation mechanism. Palmitate doses > 5 mM caused severe mitochondrial toxicity, including reduction of cell viability. Interestingly, enhancement of CoQ levels with the lowest dose of palmitate (0.15 mM) was accompanied by a significantly reduction of CoQ oxidation status, as well as low cytosolic production of reactive oxygen species. From the overall findings, it appears that CoQ response may be crucial to improve mitochondrial function and thus protect against hyperlipidemia-induced insult. These results further suggest that therapeutic agents that can stimulate endogenous levels of CoQ may be beneficial in protecting the myocardium against diabetes associated complications.