Capsaicin Protects Cardiomyocytes against Anoxia/Reoxygenation Injury via Preventing Mitochondrial Dysfunction Mediated by SIRT1

Abstract

Capsaicin (Cap) has been reported to have beneficial effects on cardiovascular system, but the mechanisms underlying these effects are still poorly understood. Apoptosis has been shown to be involved in mitochondrial dysfunction, and upregulating expression of SIRT1 can inhibit the apoptosis of cardiomyocytes induced by anoxia/reoxygenation (A/R). Therefore, the aim of this study was to test whether the protective effects of Cap against the injury to the cardiomyocytes are mediated by SIRT1. The effects of Cap with or without coadministration of sirtinol, a SIRT1 inhibitor, on changes induced by A/R in the cell viability, activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), levels of intracellular reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), related protein expression, mitochondrial permeability transition pore (mPTP) opening, and apoptosis rate in the primary neonatal rat cardiomyocytes were tested. Cap significantly increased the cell viability, upregulated expression of SIRT1 and Bcl-2, and decreased the LDH and CPK release, generation of ROS, loss of MMP, mPTP openness, activities of caspase-3, release of the cytochrome c, and apoptosis of the cardiomyocytes. Sirtinol significantly blocked the cardioprotective effects of Cap. The results suggest that the protective effects of Cap against A/R-induced injury to the cardiomyocytes are involved with SIRT1.

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes

“…2019-0036). Cardiomyocytes from 0-3 days old Sprague-Dawley rats (the Animal Center of Nanchang University, Nanchang, China) were prepared as published [7]. Briefly, hearts from neonatal rats were removed and placed in precooling D-Hank's balanced salt solution.…”

“…Culture medium after anoxia or A/R treatment was collected to evaluate the activities of lactate dehydrogenase (LDH) and creatine phosphate kinase (CK) using commercially available assay kits (Jiancheng, Nanjing, China) according to the manufacturer's instructions [7].…”

“…Flow Cytometry Assay. ROS levels were assessed with oxidation-sensitive fluorescent probe DCFH-DA (Beyotime, Shanghai, China) [7]. Cells were harvested after treatment as described in Section 2.3 and incubated with DCFH-DA at 37°C for 30 min in darkness.…”

“…Reactive oxygen species (ROS) participate in several pathophysiologic processes (e.g., cellular damage, aging, and apoptosis) during the above injury [4][5][6]. This injury causes excessive ROS generation, resulting in severe myocardial damage [3][4][5][6][7][8][9]. However, ignoring the close relationship between redox balance and ROS in cellular pathological con-ditions often prevents clinical trials from recognizing the significance of decreasing disease risk and progression.…”

“…Cap is known to have antimicrobial, analgesic, and antioxidant, among other effects [30]. Our recent studies showed that Cap upregulated 14-3-3η (a dimeric phospho-serinebinding protein involved in cardiac protection) and SIRT1 (NAD + -dependent proteins that act as gatekeepers against oxidative stress and cardiovascular injury) expression in cardiomyocytes in response to A/R injury [7,8]. The pathologic process of A/R remains unexplored.…”