Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Zhang, Dayong; Yan, Binjun; Yu, Shanshan; Zhang, Chong; Wang, Baoming; Wang, Yayan; Wang, Junbo; Yuan, Zhanggen; Zhang, Lihuang; Pan, Jianping

doi:10.1155/2015/867293

Cited by 57 publications

(52 citation statements)

References 66 publications

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“…We observed that the significant inhibitory effects on platelet function range between the concentrations of 10 and 100 µM (the highest concentration tested). These findings are consistent with other in vitro studies . However, after 24 weeks of supplementation, the plasma CoQ10 concentration in dyslipidemic patients was ≈2 µM (Figure S6, Supporting Information), at this concentration the platelet aggregation in healthy human gel‐filtered platelets was not significantly inhibited, when CoQ10 was added in vitro (Figure S10, Supporting Information).…”

Section: Discussionsupporting

confidence: 90%

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Coenzyme Q10 Upregulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth

Shi

et al. 2019

Molecular Nutrition Food Res

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Scope Platelet integrin αIIbβ3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat‐soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbβ3 signaling and thrombosis, the major cause of cardiovascular diseases. Methods and results Using a series of platelet functional assays in vitro, it is demonstrated that CoQ10 reduces human platelet aggregation, granule secretion, platelet spreading, and clot retraction. It is further demonstrated that CoQ10 inhibits platelet integrin αIIbβ3 outside‐in signaling. These inhibitory effects are mainly mediated by upregulating cAMP/PKA pathway, where CoQ10 stimulates the A2A adenosine receptor and decreases phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuates murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3)‐induced thrombosis model in vivo. Importantly, the randomized, double‐blind, placebo‐controlled clinical trial in dyslipidemic patients demonstrates that 24 weeks of CoQ10 supplementation increases platelet CoQ10 concentrations, enhances the cAMP/PKA pathway, and attenuates αIIbβ3 outside‐in signaling, leading to decreased platelet aggregation and granule release. Conclusion Through upregulating the platelet cAMP/PKA pathway, and attenuating αIIbβ3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases.

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Section: Discussionsupporting

confidence: 90%

“…For the in vitro study, concentrations of CoQ10 (1, 10, 100 µM) used were consistent with previous studies . These doses did not exert cytotoxic effects on platelets as measured by lactate dehydrogenase (LDH) leakage from platelets (Figure S1, Supporting Information).…”

Section: Methodssupporting

confidence: 77%

Coenzyme Q10 Upregulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth

Shi

et al. 2019

Molecular Nutrition Food Res

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“…As shown in previous studies on tissues or cells from other organs, Q10 treatment on doxorubicin challenged SD resulted in regulation of pro-apoptotic proteins and thereby inhibited apoptosis, Q10 also increased survival protein expression to enhances cell survival by acting as an effective antioxidant (Chen et al, 2011;Navas et al, 2002;Zhang et al, 2015).…”

Section: Discussionsupporting

confidence: 62%

Protective effect of Co‐enzyme Q10 On doxorubicin‐induced cardiomyopathy of rat hearts

Chen

Hou

Shibu

et al. 2016

Environmental Toxicology

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Q10 is a powerful antioxidant often used in medical nutritional supplements for cancer treatment. This study determined whether Q10 could effectively prevent cardio-toxicity caused by doxorubicin treatment. Four week old SD rats were segregated into groups namely control, doxorubicin group (challenged with doxorubicin), Dox + Q10 group (with doxorubicin challenge and oral Q10 treatment), and Q10 group (with oral Q10 treatment). Doxorubicin groups received IP doxorubicin (2.5 mg/kg) every 3 days and Q10 groups received Q10 (10 mg/kg) every day. Three weeks of doxorubicin challenge caused significant reduction in heart weight, disarray in cardiomyocyte arrangement, elevation of collagen accumulation, enhancement of fibrosis and cell death associated proteins, and inhibition of survival proteins. However, Q10 effectively protected cardiomyocytes and ameliorated fibrosis and cell death induced by doxorubicin. Q10 is, therefore, evidently a potential drug to prevent heart damage caused by doxorubicin. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 679-689, 2017.

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“…Recent studies have linked activation of the Akt and mTOR signaling pathways with the production of ROS and altered cell viability [31]. As shown in Figure 6, cells grown in galactose exhibited increased Akt and mTOR phosphorylation as compared to glucose-grown cells.…”

Section: Glucose Oxidation and Protection Against Ischemia-reperfusiomentioning

confidence: 94%

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production

et al. 2020

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After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.

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Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Cited by 57 publications

References 66 publications

Coenzyme Q10 Upregulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth

Coenzyme Q10 Upregulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth

Protective effect of Co‐enzyme Q10 On doxorubicin‐induced cardiomyopathy of rat hearts

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production

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