Coenzyme Q10 Protects Astrocytes from ROS-Induced Damage through Inhibition of Mitochondria-Mediated Cell Death Pathway

Abstract

Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species to protect neuronal cells against oxidative stress in neurodegenerative diseases. The present study was designed to examine whether CoQ10 was capable of protecting astrocytes from reactive oxygen species (ROS) mediated damage. For this purpose, ultraviolet B (UVB) irradiation was used as a tool to induce ROS stress to cultured astrocytes. The cells were treated with 10 and 25 μg/ml of CoQ10 for 3 or 24 h prior to the cells being exposed to UVB irradiation and maintained for 24 h post UVB exposure. Cell viability was assessed by MTT conversion assay. Mitochondrial respiration was assessed by respirometer. While superoxide production and mitochondrial membrane potential were measured using fluorescent probes, levels of cytochrome C (cyto-c), cleaved caspase-9, and caspase-8 were detected using Western blotting and/or immunocytochemistry. The results showed that UVB irradiation decreased cell viability and this damaging effect was associated with superoxide accumulation, mitochondrial membrane potential hyperpolarization, mitochondrial respiration suppression, cyto-c release, and the activation of both caspase-9 and -8. Treatment with CoQ10 at two different concentrations started 24 h before UVB exposure significantly increased the cell viability. The protective effect of CoQ10 was associated with reduction in superoxide, normalization of mitochondrial membrane potential, improvement of mitochondrial respiration, inhibition of cyto-c release, suppression of caspase-9. Furthermore, CoQ10 enhanced mitochondrial biogenesis. It is concluded that CoQ10 may protect astrocytes through suppression of oxidative stress, prevention of mitochondrial dysfunction, blockade of mitochondria-mediated cell death pathway, and enhancement of mitochondrial biogenesis.

The use of antioxidants in the treatment of traumatic brain injury

“…The target of this antioxidant is the inner mitochondrial membrane (Zaki 2016), making ubiquinol an antioxidant that could potentially ameliorate secondary injury after a TBI. Specifically, ubiquinol decreases the production of ROS, which prevents mitochondrial dysfunction by stabilizing the membranes and improving energy production and biogenesis, as well as inhibiting cell death via pathways in the mitochondria (Jing et al 2015). As an antioxidant that targets the inner mitochondrial membrane, ubiquinol could be a supplemental treatment to decrease the severity of secondary injury after TBI.…”

“…These antioxidants combat oxidative stress by ameliorating the overproduction of ROS and preventing mitochondrial DNA damage (Schmelzer & Doring 2012). Another important antioxidant that occurs naturally in the body is ubiquinol, the reduced form of CoQ10, which can protect neuronal cells from oxidative stress (Jing et al 2015). After age 40, mitochondrial capacity to reduce ubiquinone to ubiquinol progressively declines (Olivieri et al 2013).…”

“…Another important antioxidant that occurs naturally in the body is ubiquinol, the reduced form of CoQ10, which can protect neuronal cells from oxidative stress (Jing et al . ). After age 40, mitochondrial capacity to reduce ubiquinone to ubiquinol progressively declines (Olivieri et al .…”

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

“…A number of studies have demonstrated that the apoptotic pathway is the most important mechanism involved in the process of killing malignant cells with anticarcinogens (32,33). Several studies have also shown that OSW-1 can induce calcium-or caspase-8-dependent cleavage of Bcl-2-mediated apoptosis (34,35).…”

PARP1 Inhibition Augments UVB-Mediated Mitochondrial Changes—Implications for UV-Induced DNA Repair and Photocarcinogenesis

“…PARP inhibitors became valuable tools in treating cancer cells harboring DNA repair defect with the combination of either radio-or chemotherapy [39][40][41]. In addition to several orally-administered PARP inhibitors that are under active clinical development, recently ABT-888 (veliparib) has emerged as an effective drug in treating various solid tumors [42] partially via modulating mitochondrial activity [43,44].Although UV radiation has been shown to trigger morphological [45,46] and functional changes of mitochondria [47][48][49], published data led to contradictory results most likely due to the diversity of applied UV spectrum, UV dose, and cell type. Studies using UVC irradiation revealed that UVC induced mitochondrial hyperfusion and resulted in enhanced ATP synthesis via oxidative phosphorylation (OXPHOS) [50].…”