title: Coenzyme Q10 ameliorates oxidative stress and prevents mitochondrial alteration in ischemic retinal injury.
abstract: Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species for protecting neuronal cells against oxidative stress in neurodegenerative diseases. We tested whether a diet supplemented with CoQ10 ameliorates oxidative stress and mitochondrial alteration, as well as promotes retinal ganglion cell (RGC) survival in ischemic retina induced by intraocular pressure elevation. A CoQ10 significantly promoted RGC survival at 2 weeks after ischemia. Superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) expression were significantly increased at 12 h after ischemic injury. In contrast, the CoQ10 significantly prevented the upregulation of SOD2 and HO-1 protein expression in ischemic retina. In addition, the CoQ10 significantly blocked activation of astroglial and microglial cells in ischemic retina. Interestingly, the CoQ10 blocked apoptosis by decreasing caspase-3 protein expression in ischemic retina. Bax and phosphorylated Bad (pBad) protein expression were significantly increased in ischemic retina at 12 h. Interestingly, while CoQ10 significantly decreased Bax protein expression in ischemic retina, CoQ10 showed greater increase of pBad protein expression. Of interest, ischemic injury significantly increased mitochondrial transcription factor A (Tfam) protein expression in the retina at 12 h, however, CoQ10 significantly preserved Tfam protein expression in ischemic retina. Interestingly, there were no differences in mitochondrial DNA content among control- or CoQ10-treated groups. Our findings demonstrate that CoQ10 protects RGCs against oxidative stress by modulating the Bax/Bad-mediated mitochondrial apoptotic pathway as well as prevents mitochondrial alteration by preserving Tfam protein expression in ischemic retina. Our results suggest that CoQ10 may provide neuroprotection against oxidative stress-mediated mitochondrial alterations in ischemic retinal injury.
authors: Laboratory for Optic Nerve Biology, Department of Ophthalmology, Hamilton Glaucoma Center, University of California San Diego, 9415 Campus Point Drive, La Jolla, CA, 92037, USA.
authors: Dongwook
authors: D
authors: Lee
authors: Keun-Young
authors: KY
authors: Kim
authors: Myoung Sup
authors: MS
authors: Shim
authors: Sang Yeop
authors: SY
authors: Kim
authors: Mark H
authors: MH
authors: Ellisman
authors: Robert N
authors: RN
authors: Weinreb
authors: Won-Kyu
authors: WK
authors: Ju
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005260:Female; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: C494820:Bad protein, mouse; C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018696:Neuroprotective Agents; C081930:Tfam protein, mouse; D014815:Vitamins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D014451:Ubiquinone; C024989:coenzyme Q10