View Item 

Show simple item record

Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability
dc.contributor.authorDu, Yunpeng
dc.contributor.authorCramer, Megan
dc.contributor.authorLee, Chieh Allen
dc.contributor.authorTang, Jie
dc.contributor.authorMuthusamy, Arivalagan
dc.contributor.authorAntonetti, David A.
dc.contributor.authorJin, Hui
dc.contributor.authorPalczewski, Krzysztof
dc.contributor.authorKern, Timothy S.
dc.date.accessioned2020-03-17T18:35:03Z
dc.date.available2020-03-17T18:35:03Z
dc.date.issued2015-05
dc.identifier.citationDu, Yunpeng; Cramer, Megan; Lee, Chieh Allen; Tang, Jie; Muthusamy, Arivalagan; Antonetti, David A.; Jin, Hui; Palczewski, Krzysztof; Kern, Timothy S. (2015). "Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability." The FASEB Journal 29(5): 2194-2204.
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.urihttps://hdl.handle.net/2027.42/154521
dc.description.abstractReactive oxygen species play an important role in the pathogenesis of diabetic retinopathy. We studied the role of adrenergic and serotonin receptors in the generation of superoxide by retina and 661W retinal cells in high glucose and of the α1‐adrenergic receptor (AR) on vascular lesions of the retinopathy in experimentally diabetic C57Bl/6J mice (and controls) after 2 and 8 months. Compared with 5 mM glucose, incubating cells or retinal explants in 30 mM glucose induced superoxide generation. This response was reduced or ablated by pharmacologic inhibition of the α1‐AR (a Gq‐coupled receptor) or Gs‐coupled serotonin (5‐HT2, 5‐HT4, 5‐HT6, and 5‐HT7) receptors or by activation of the Gi‐coupled α2‐AR. In elevated glucose, the α1‐AR produced superoxide via phospholipase C, inositol triphosphate‐induced Ca2+ release, and NADPH oxidase, and pharmacologic inhibition of these reactions prevented the superoxide increase. Generation of retinal superoxide, expression of proinflammatory proteins, and degeneration of retinal capillaries in diabetes all were significantly inhibited with daily doxazosin or apocynin (inhibitors of α1‐AR and NADPH oxidase, respectively), but increased vascular permeability was not significantly affected. Adrenergic receptors, and perhaps other GPCRs, represent novel targets for inhibiting the development of important features of diabetic retinopathy.—Du, Y., Cramer, M., Lee, C. A., Tang, J., Muthusamy, A., Antonetti, D. A., Jin, H., Palczewski, K., Kern, T. S. Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability. FASEB J. 29, 2194‐2204 (2015). www.fasebj.org
dc.publisherWiley Periodicals, Inc.
dc.publisherFederation of American Societies for Experimental Biology
dc.subject.otherGPCRs
dc.subject.otherinflammation
dc.subject.otherdiabetic retinopathy
dc.subject.otherNADPH oxidase
dc.titleAdrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelBiology
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154521/1/fsb2fj14269431.pdf
dc.identifier.doi10.1096/fj.14-269431
dc.identifier.sourceThe FASEB Journal
dc.identifier.citedreferencePrabu, S. K., Anandatheerthavarada, H. K., Raza, H., Srinivasan, S., Spear, J. F., and Avadhani, N. G. ( 2006 ) Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. J. Biol. Chem. 281, 2061 – 2070
dc.identifier.citedreferenceBrown, G. C. ( 2007 ) Mechanisms of inflammatory neurodegeneration: iNOS and NADPH oxidase. Biochem. Soc. Trans. 35, 1119 – 1121
dc.identifier.citedreferenceYamamori, T., Inanami, O., Nagahata, H., Cui, Y., and Kuwabara, M. ( 2000 ) Roles of p38 MAPK, PKC and PI3-K in the signaling pathways of NADPH oxidase activation and phagocytosis in bovine polymorphonuclear leukocytes. FEBS Lett. 467, 253 – 258
dc.identifier.citedreferenceAl-Shabrawey, M., Bartoli, M., El-Remessy, A. B., Ma, G., Matragoon, S., Lemtalsi, T., Caldwell, R. W., and Caldwell, R. B. ( 2008 ) Role of NADPH oxidase and Stat3 in statin-mediated protection against diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 49, 3231 – 3238
dc.identifier.citedreferenceWilkinson-Berka, J. L., Deliyanti, D., Rana, I., Miller, A. G., Agrotis, A., Armani, R., Szyndralewiez, C., Wingler, K., Touyz, R. M., Cooper, M. E., Jandeleit-Dahm, K. A., and Schmidt, H. H. ( 2014 ) NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy. Antioxid. Redox Signal. 20, 2726 – 2740
dc.identifier.citedreferenceGray, S. P., Di Marco, E., Okabe, J., Szyndralewiez, C., Heitz, F., Montezano, A. C., de Haan, J. B., Koulis, C., El-Osta, A., Andrews, K. L., Chin-Dusting, J. P., Touyz, R. M., Wingler, K., Cooper, M. E., Schmidt, H. H., and Jandeleit-Dahm, K. A. ( 2013 ) NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 127, 1888 – 1902
dc.identifier.citedreferenceSedeek, M., Nasrallah, R., Touyz, R. M., and Hébert, R. L. ( 2013 ) NADPH oxidases, reactive oxygen species, and the kidney: friend and foe. J. Am. Soc. Nephrol. 24, 1512 – 1518
dc.identifier.citedreferenceChan, E. C., van Wijngaarden, P., Liu, G. S., Jiang, F., Peshavariya, H., and Dusting, G.J. ( 2013 ) Involvement of Nox2 NADPH oxidase in retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 54, 7061 – 7067
dc.identifier.citedreferenceSuzuki, F., Taniguchi, T., Nakamura, S., Akagi, Y., Kubota, C., Satoh, M., and Muramatsu, I. ( 2002 ) Distribution of alpha-1 adrenoceptor subtypes in RNA and protein in rabbit eyes. Br. J. Pharmacol. 135, 600 – 608
dc.identifier.citedreferenceZarbin, M. A., Wamsley, J. K., Palacios, J. M., and Kuhar, M.J. ( 1986 ) Autoradiographic localization of high affinity GABA, benzodiazepine, dopaminergic, adrenergic and muscarinic cholinergic receptors in the rat, monkey and human retina. Brain Res. 374, 75 – 92
dc.identifier.citedreferenceWoldemussie, E., Wijono, M., and Pow, D. ( 2007 ) Localization of alpha 2 receptors in ocular tissues. Vis. Neurosci. 24, 745 – 756
dc.identifier.citedreferenceJiang, Y., Walker, R. J., Kern, T. S., and Steinle, J. J. ( 2010 ) Application of isoproterenol inhibits diabetic-like changes in the rat retina. Exp. Eye Res. 91, 171 – 179
dc.identifier.citedreferenceSteinle, J. J., Chin, V. C., Williams, K. P., and Panjala, S. R. ( 2008 ) Beta-adrenergic receptor stimulation modulates iNOS protein levels through p38 and ERK1/2 signaling in human retinal endothelial cells. Exp. Eye Res. 87, 30 – 34
dc.identifier.citedreferenceWalker, R. J., and Steinle, J. J. ( 2007 ) Role of beta-adrenergic receptors in inflammatory marker expression in Müller cells. Invest. Ophthalmol. Vis. Sci. 48, 5276 – 5281
dc.identifier.citedreferenceJiang, Y., and Steinle, J. J. ( 2010 ) Systemic propranolol reduces b-wave amplitude in the ERG and increases IGF-1 receptor phosphorylation in rat retina. Invest. Ophthalmol. Vis. Sci. 51, 2730 – 2735
dc.identifier.citedreferenceJiang, Y., Zhang, Q., Liu, L., Tang, J., Kern, T. S., and Steinle, J. J. ( 2013 ) β2-adrenergic receptor knockout mice exhibit A diabetic retinopathy phenotype. PLoS ONE 8, e70555
dc.identifier.citedreferenceKusari, J., Zhou, S. X., Padillo, E., Clarke, K. G., and Gil, D. W. ( 2010 ) Inhibition of vitreoretinal VEGF elevation and blood-retinal barrier breakdown in streptozotocin-induced diabetic rats by brimonidine. Invest. Ophthalmol. Vis. Sci. 51, 1044 – 1051
dc.identifier.citedreferenceHadjiconstantinou, M., Qu, Z. X., Moroi-Fetters, S. E., and Neff, N. H. ( 1988 ) Apparent loss of Gi protein activity in the diabetic retina. Eur. J. Pharmacol. 149, 193 – 194
dc.identifier.citedreferenceLivingstone, C., McLellan, A. R., McGregor, M. A., Wilson, A., Connell, J. M., Small, M., Milligan, G., Paterson, K. R., and Houslay, M. D. ( 1991 ) Altered G-protein expression and adenylate cyclase activity in platelets of non-insulin-dependent diabetic (NIDDM) male subjects. Biochim. Biophys. Acta 1096, 127 – 133
dc.identifier.citedreferenceAbbracchio, M. P., Cattabeni, F., Di Giulio, A. M., Finco, C., Paoletti, A. M., Tenconi, B., and Gorio, A. ( 1991 ) Early alterations of Gi/Go protein-dependent transductional processes in the retina of diabetic animals. J. Neurosci. Res. 29, 196 – 200
dc.identifier.citedreferenceDescorbeth, M., and Anand-Srivastava, M. B. ( 2010 ) Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11α proteins and associated signaling in vascular smooth muscle cells. Free Radic. Biol. Med. 49, 1395 – 1405
dc.identifier.citedreferenceLi, Y., Lappas, G., and Anand-Srivastava, M. B. ( 2007 ) Role of oxidative stress in angiotensin II-induced enhanced expression of Gi(alpha) proteins and adenylyl cyclase signaling in A10 vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 292, H1922 – H1930
dc.identifier.citedreferenceLi, Y., Descorbeth, M., and Anand-Srivastava, M. B. ( 2008 ) Role of oxidative stress in high glucose-induced decreased expression of Gialpha proteins and adenylyl cyclase signaling in vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 294, H2845 – H2854
dc.identifier.citedreferenceGoraya, T. Y., Wilkins, P., Douglas, J. G., Zhou, J., and Berti-Mattera, L. N. ( 1995 ) Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats. J. Neurosci. Res. 41, 518 – 525
dc.identifier.citedreferenceKanwar, M., and Kowluru, R. A. ( 2008 ) Diabetes regulates small molecular weight G-protein, H-Ras, in the microvasculature of the retina: implication in the development of retinopathy. Microvasc. Res. 76, 189 – 193
dc.identifier.citedreferenceDo Carmo Buonfiglio, D., Peliciari-Garcia, R. A., do Amaral, F. G., Peres, R., Nogueira, T. C., Afeche, S. C., and Cipolla-Neto, J. ( 2011 ) Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats. Invest. Ophthalmol. Vis. Sci. 52, 7416 – 7422
dc.identifier.citedreferenceChang, J. C., Ciaccio, P., Schroeder, P., Wright, L., Westwood, R., and Berg, A. L. ( 2014 ) Pathology and neurotoxicity in dogs after repeat dose exposure to a serotonin 5-HT1B inhibitor. J. Toxicol. Pathol. 27, 31 – 42
dc.identifier.citedreferenceGavras, I., and Gavras, H. ( 2001 ) Benefits and side effects of blood pressure lowering treatment: what was wrong with doxazosin in the ALLHAT? Curr. Control. Trials Cardiovasc. Med. 2, 257 – 259
dc.identifier.citedreferenceFredriksson, R., Lagerström, M. C., Lundin, L. G., and Schiöth, H. B. ( 2003 ) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256 – 1272
dc.identifier.citedreferenceMarinissen, M. J., and Gutkind, J. S. ( 2001 ) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol. Sci. 22, 368 – 376
dc.identifier.citedreferenceChen, Y., Palczewska, G., Mustafi, D., Golczak, M., Dong, Z., Sawada, O., Maeda, T., Maeda, A., and Palczewski, K. ( 2013 ) Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration. J. Clin. Invest. 123, 5119 – 5134
dc.identifier.citedreferenceUsui, S., Oveson, B. C., Lee, S. Y., Jo, Y. J., Yoshida, T., Miki, A., Miki, K., Iwase, T., Lu, L., and Campochiaro, P. A. ( 2009 ) NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa. J. Neurochem. 110, 1028 – 1037
dc.identifier.citedreferenceChen, Y., Okano, K., Maeda, T., Chauhan, V., Golczak, M., Maeda, A., and Palczewski, K. ( 2012 ) Mechanism of all-trans-retinal toxicity with implications for stargardt disease and age-related macular degeneration. J. Biol. Chem. 287, 5059 – 5069
dc.identifier.citedreferenceKowluru, R. A., Tang, J., and Kern, T. S. ( 2001 ) Abnormalities of retinal metabolism in diabetes and experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes 50, 1938 – 1942
dc.identifier.citedreferenceKanwar, M., Chan, P. S., Kern, T. S., and Kowluru, R. A. ( 2007 ) Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase. Invest. Ophthalmol. Vis. Sci. 48, 3805 – 3811
dc.identifier.citedreferenceBerkowitz, B. A., Gradianu, M., Bissig, D., Kern, T. S., and Roberts, R. ( 2009 ) Retinal ion regulation in a mouse model of diabetic retinopathy: natural history and the effect of Cu/Zn superoxide dismutase overexpression. Invest. Ophthalmol. Vis. Sci. 50, 2351 – 2358
dc.identifier.citedreferenceDu, Y., Veenstra, A., Palczewski, K., and Kern, T. S. ( 2013 ) Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina. Proc. Natl. Acad. Sci. USA 110, 16586 – 16591
dc.identifier.citedreferenceBillington, C. K., and Hall, I. P. ( 2012 ) Novel cAMP signalling paradigms: therapeutic implications for airway disease. Br. J. Pharmacol. 166, 401 – 410
dc.identifier.citedreferenceCollier, R. J., Wang, Y., Smith, S. S., Martin, E., Ornberg, R., Rhoades, K., and Romano, C. ( 2011 ) Complement deposition and microglial activation in the outer retina in light-induced retinopathy: inhibition by a 5-HT1A agonist. Invest. Ophthalmol. Vis. Sci. 52, 8108 – 8116
dc.identifier.citedreferenceCollier, R. J., Patel, Y., Martin, E. A., Dembinska, O., Hellberg, M., Krueger, D. S., Kapin, M. A., and Romano, C. ( 2011 ) Agonists at the serotonin receptor (5-HT(1A)) protect the retina from severe photo-oxidative stress. Invest. Ophthalmol. Vis. Sci. 52, 2118 – 2126
dc.identifier.citedreferenceShen, J., Ghai, K., Sompol, P., Liu, X., Cao, X., Iuvone, P. M., and Ye, K. ( 2012 ) N-acetyl serotonin derivatives as potent neuroprotectants for retinas. Proc. Natl. Acad. Sci. USA 109, 3540 – 3545
dc.identifier.citedreferenceThampi, P., Rao, H. V., Mitter, S. K., Cai, J., Mao, H., Li, H., Seo, S., Qi, X., Lewin, A. S., Romano, C., and Boulton, M. E. ( 2012 ) The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium. PLoS ONE 7, e34468
dc.identifier.citedreferenceRenganathan, K., Gu, J., Rayborn, M. E., Crabb, J. S., Salomon, R. G., Collier, R. J., Kapin, M. A., Romano, C., Hollyfield, J. G., and Crabb, J. W. ( 2013 ) CEP biomarkers as potential tools for monitoring therapeutics. PLoS ONE 8, e76325
dc.identifier.citedreferenceal-Ubaidi, M. R., Font, R. L., Quiambao, A. B., Keener, M. J., Liou, G. I., Overbeek, P. A., and Baehr, W. ( 1992 ) Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. J. Cell Biol. 119, 1681 – 1687
dc.identifier.citedreferenceLee, C. A., Li, G., Patel, M. D., Petrash, J. M., Benetz, B. A., Veenstra, A., Amengual, J., Von Lintig, J., Burant, C., Tang, J., and Kern, T. S. ( 2013 ) Diabetes-induced impairment in visual function in mice: contributions of p38 MAPK, RAGE, leukocytes, and aldose reductase. Invest. Ophthalmol. Vis. Sci. 93, 135 – 143
dc.identifier.citedreferenceTang, J., Allen Lee, C., Du, Y., Sun, Y., Pearlman, E., Sheibani, N., and Kern, T. S. ( 2013 ) MyD88-dependent pathways in leukocytes affect the retina in diabetes. PLoS ONE 8, e68871
dc.identifier.citedreferenceDu, Y., Tang, J., Li, G., Berti-Mattera, L., Lee, C. A., Bartkowski, D., Gale, D., Monahan, J., Niesman, M. R., Alton, G., and Kern, T. S. ( 2010 ) Effects of p38 MAPK inhibition on early stages of diabetic retinopathy and sensory nerve function. Invest. Ophthalmol. Vis. Sci. 51, 2158 – 2164
dc.identifier.citedreferenceKern, T. S., Du, Y., Miller, C. M., Hatala, D. A., and Levin, L. A. ( 2010 ) Overexpression of Bcl-2 in vascular endothelium inhibits the microvascular lesions of diabetic retinopathy. Am. J. Pathol. 176, 2550 – 2558
dc.identifier.citedreferenceGubitosi-Klug, R. A., Talahalli, R., Du, Y., Nadler, J. L., and Kern, T. S. ( 2008 ) 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes 57, 1387 – 1393
dc.identifier.citedreferenceKern, T. S., Miller, C. M., Du, Y., Zheng, L., Mohr, S., Ball, S. L., Kim, M., Jamison, J. A., and Bingaman, D. P. ( 2007 ) Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology. Diabetes 56, 373 – 379
dc.identifier.citedreferenceDu, Y., Miller, C. M., and Kern, T. S. ( 2003 ) Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radic. Biol. Med. 35, 1491 – 1499
dc.identifier.citedreferenceBest, T. M., Fiebig, R., Corr, D. T., Brickson, S., and Ji, L. ( 1999 ) Free radical activity, antioxidant enzyme, and glutathione changes with muscle stretch injury in rabbits. J. Appl. Physiol. 87, 74 – 82
dc.identifier.citedreferenceAntonetti, D. A., Barber, A. J., Khin, S., Lieth, E., Tarbell, J. M., and Gardner, T. W.; Penn State Retina Research Group. ( 1998 ) Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Diabetes 47, 1953 – 1959
dc.identifier.citedreferenceLi, G., Tang, J., Du, Y., Lee, C. A., and Kern, T. S. ( 2011 ) Beneficial effects of RAGE-Ig fusion protein on early diabetic retinopathy and tactile allodynia. Mol. Vis. 17, 3156 – 3165
dc.identifier.citedreferenceLi, G., Veenstra, A. A., Talahalli, R. R., Wang, X., Gubitosi-Klug, R. A., Sheibani, N., and Kern, T. S. ( 2012 ) Marrow-derived cells regulate the development of early diabetic retinopathy and tactile allodynia in mice. Diabetes 61, 3294 – 3303
dc.identifier.citedreferenceVeenstra, A. A., Tang, J., and Kern, T. S. ( 2013 ) Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy. PLoS ONE 8, e78405
dc.identifier.citedreferenceAl-Shabrawey, M., Rojas, M., Sanders, T., Behzadian, A., El-Remessy, A., Bartoli, M., Parpia, A. K., Liou, G., and Caldwell, R. B. ( 2008 ) Role of NADPH oxidase in retinal vascular inflammation. Invest. Ophthalmol. Vis. Sci. 49, 3239 – 3244
dc.identifier.citedreferenceZheng, L., Du, Y., Miller, C., Gubitosi-Klug, R. A., Ball, S., Berkowitz, B. A., and Kern, T. S. ( 2007 ) Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes. Diabetologia 50, 1987 – 1996
dc.identifier.citedreferenceElms, S. C., Toque, H. A., Rojas, M., Xu, Z., Caldwell, R. W., and Caldwell, R. B. ( 2013 ) The role of arginase I in diabetes-induced retinal vascular dysfunction in mouse and rat models of diabetes. Diabetologia 56, 654 – 662
dc.identifier.citedreferenceTang, J., Du, Y., Petrash, J. M., Sheibani, N., and Kern, T. S. ( 2013 ) Deletion of aldose reductase from mice inhibits diabetes-induced retinal capillary degeneration and superoxide generation. PLoS ONE 8, e62081
dc.identifier.citedreferenceInoue, T., Suzuki, Y., Yoshimaru, T., and Ra, C. ( 2008 ) Reactive oxygen species produced up- or downstream of calcium influx regulate proinflammatory mediator release from mast cells: role of NADPH oxidase and mitochondria. Biochim. Biophys. Acta 1783, 789 – 802
dc.owningcollnameInterdisciplinary and Peer-Reviewed


Files in this item

Name:
fsb2fj14269431.pdf
Size:
1.017MB
Format:
PDF
View/Open

Show simple item record

Remediation of Harmful Language

The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.

Accessibility

If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.