title: Ubisol-Q10 Prevents Glutamate-Induced Cell Death by Blocking Mitochondrial Fragmentation and Permeability Transition Pore Opening.
abstract: Mitochondrial dysfunction and oxidative stress are the major events that lead to the formation of mitochondrial permeability transition pore (mPTP) during glutamate-induced cytotoxicity and cell death. Coenzyme Q10 (CoQ10) has widely been used for the treatment of mitochondrial disorders and neurodegenerative diseases. Comparing to traditional lipid-soluble CoQ10, water soluble CoQ10 (Ubisol-Q10) has high intracellular and intra-mitochondrial distribution. The aims of the present study are to determine the neuroprotective effects of Ubisol-Q10 on glutamate-induced cell death and to explore its functional mechanisms. HT22 neuronal cells were exposed to glutamate. Cell viability was measured and mitochondrial fragmentation was assessed by mitochondrial imaging. The mPTP opening was determined by mitochondrial membrane potential and calcium retention capacity. The results revealed that the anti-glutamate toxicity effects of Ubisol-Q10 was associated with its ability to block mitochondrial fragmentation, to maintain calcium retention capacity and mitochondrial membrane potential, and to prevent mPTP formation, AIF release, and DNA fragmentation. We concluded that Ubisol-Q10 protects cells from glutamate toxicity by preserving the integrity of mitochondrial structure and function. Therefore, adequate CoQ10 supplementation may be beneficial in preventing cerebral stroke and other disorders that involve mitochondrial dysfunction.
authors.affiliation: 1. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE) College of Art and Science, North Carolina Central University, Durham, NC 27707, USA;; 4. Department of Medicine, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumari
authors.affiliation: 1. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE) College of Art and Science, North Carolina Central University, Durham, NC 27707, USA;; 3. Department of Neurological Surgery, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53792, USA;
authors.forename: Suresh L
authors.initials: SL
authors.lastname: Mehta
authors.affiliation: 2. Department of Mathematics and Computer Science, North Carolina Central University, Durham, NC 27707, USA;
authors.forename: Gaolin Z
authors.initials: GZ
authors.lastname: Milledge
authors.affiliation: 2. Department of Mathematics and Computer Science, North Carolina Central University, Durham, NC 27707, USA;
authors.forename: Xinyu
authors.initials: X
authors.lastname: Huang
authors.affiliation: 5. Neurological Center of the General Hospital of Ningxia Medical University, Ningxia Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, P.R. China.
authors.forename: Haining
authors.initials: H
authors.lastname: Li
authors.affiliation: 1. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE) College of Art and Science, North Carolina Central University, Durham, NC 27707, USA;
authors.forename: P Andy
authors.initials: PA
authors.lastname: Li
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D014451:Ubiquinone; D018698:Glutamic Acid; C024989:coenzyme Q10
keywords: AIF; Coenzyme Q10; calcium retention.; glutamate toxicity; mitochondrial fragmentation; neuronal cell death