Brimonidine Blocks Glutamate Excitotoxicity-Induced Oxidative Stress and Preserves Mitochondrial Transcription Factor A in Ischemic Retinal Injury
| Autor: | James D. Lindsey, Dongwook Lee, Keunyoung Kim, You Hyun Noh, Robert N. Weinreb, Won-Kyu Ju, Stephen Chai, Mark H. Ellisman |
|---|---|
| Přispěvatelé: | Barnes, Steven |
| Rok vydání: | 2012 |
| Předmět: |
Retinal Ganglion Cells
Anatomy and Physiology genetic structures Excitotoxicity lcsh:Medicine Neurodegenerative Eye medicine.disease_cause Biochemistry Oxidative Phosphorylation Energy-Producing Processes 0302 clinical medicine Ischemia Receptors Molecular Cell Biology Adrenergic alpha-2 Receptor Agonists lcsh:Science Energy-Producing Organelles bcl-2-Associated X Protein 0303 health sciences Multidisciplinary Chemistry Glutamate receptor Neurochemistry alpha-2 Signaling Cascades DNA-Binding Proteins medicine.anatomical_structure 5.1 Pharmaceuticals Adrenergic Brimonidine Tartrate Cytochemistry Medicine Retinal Disorders bcl-Associated Death Protein Development of treatments and therapeutic interventions Neurochemicals Glutamate N-Methyl-D-Aspartate Research Article Signal Transduction medicine.medical_specialty General Science & Technology Glutamic Acid Outer plexiform layer Bioenergetics Receptors N-Methyl-D-Aspartate Retinal ganglion Neuroprotection Retina Stress Signaling Cascade Mitochondrial Proteins 03 medical and health sciences Retinal Diseases Receptors Adrenergic alpha-2 Quinoxalines Internal medicine medicine Animals Eye Disease and Disorders of Vision Biology Ganglion cell layer 030304 developmental biology Superoxide Dismutase lcsh:R Neurosciences Glaucoma TFAM Inner plexiform layer eye diseases Rats Oxidative Stress Ophthalmology Endocrinology Cellular Neuroscience 030221 ophthalmology & optometry lcsh:Q sense organs Molecular Neuroscience Physiological Processes Energy Metabolism Transcription Factors Neuroscience |
| Zdroj: | PLoS ONE PloS one, vol 7, iss 10 Lee, D; Kim, KY; Noh, YH; Chai, S; Lindsey, JD; Ellisman, MH; et al.(2012). Brimonidine Blocks Glutamate Excitotoxicity-Induced Oxidative Stress and Preserves Mitochondrial Transcription Factor A in Ischemic Retinal Injury. PLoS ONE, 7(10). doi: 10.1371/journal.pone.0047098. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/25s8z7mz PLoS ONE, Vol 7, Iss 10, p e47098 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Glutamate excitotoxicity-induced oxidative stress have been linked to mitochondrial dysfunction in retinal ischemia and optic neuropathies including glaucoma. Brimonindine (BMD), an alpha 2-adrenergic receptor agonist, contributes to the neuroprotection of retinal ganglion cells (RGCs) against glutamate excitotoxicity or oxidative stress. However, the molecular mechanisms of BMD-associated mitochondrial preservation in RGC protection against glutamate excitotoxicity-induced oxidative stress following retinal ischemic injury remain largely unknown. Here, we tested whether activation of alpha 2 adrenergic receptor by systemic BMD treatment blocks glutamate excitotoxicity-induced oxidative stress, and preserves the expression of mitochondrial transcription factor A (Tfam) and oxidative phosphorylation (OXPHOS) complex in ischemic retina. Sprague-Dawley rats received BMD (1 mg/kg/day) or vehicle (0.9% saline) systemically and then transient ischemia was induced by acute intraocular pressure elevation. Systemic BMD treatment significantly increased RGC survival at 4 weeks after ischemia. At 24 hours, BMD significantly decreased Bax expression but increased Bcl-xL and phosphorylated Bad protein expression in ischemic retina. Importantly. BMD significantly blocked the upregulations of N-methyl-D-aspartate receptors 1 and 2A protein expression, as well as of SOD2 protein expression in ischemic retina at 24 hours. During the early neurodegeneration following ischemic injury (12-72 hours), Tfam and OXPHOS complex protein expression were significantly increased in vehicle-treated retina. At 24 hours after ischemia, Tfam immunoreactivity was increased in the outer plexiform layer, inner nuclear layer, inner plexiform layer and ganglion cell layer. Further, Tfam protein was expressed predominantly in RGCs. Finally, BMD preserved Tfam immunoreactivity in RGCs as well as Tfam/OXPHOS complex protein expression in the retinal extracts against ischemic injury. Our findings suggest that systemic BMD treatment protects RGCs by blockade of glutamate excitotoxicity-induced oxidative stress and subsequent preservation of Tfam/OXPHOS complex expression in ischemic retina. © 2012 Lee et al. |
| Databáze: | OpenAIRE |
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