Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zheng, L.
Right arrow Articles by Kern, T. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zheng, L.
Right arrow Articles by Kern, T. S.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:2960-2967, 2004
© 2004 by the American Diabetes Association, Inc.

Poly(ADP-Ribose) Polymerase Is Involved in the Development of Diabetic Retinopathy via Regulation of Nuclear Factor-{kappa}B

Ling Zheng1, Csaba Szabó2, and Timothy S. Kern1,3

1 Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio
2 Inotek Pharmaceuticals, Beverly, Massachusetts
3 Department of Medicine, Center for Diabetes Research, Case Western Reserve University, Cleveland, Ohio

The current study investigated the role of poly(ADP-ribose) polymerase (PARP) in the development of diabetic retinopathy. Activity of PARP was increased in whole retina and in endothelial cells and pericytes of diabetic rats. Administration of PJ-34 (a potent PARP inhibitor) for 9 months to diabetic rats significantly inhibited the diabetes-induced death of retinal microvascular cells and the development of early lesions of diabetic retinopathy, including acellular capillaries and pericyte ghosts. To further investigate how PARP activation leads to cell death in diabetes, we investigated the possibility that PARP acts as a coactivator of nuclear factor-{kappa}B (NF-{kappa}B) in the retinal cells. In bovine retinal endothelial cells (BRECs), PARP interacted directly with both subunits of NF-{kappa}B (p50 and p65). More PARP was complexed to the p50 subunit in elevated glucose concentration (25 mmol/l) than at 5 mmol/l glucose. PJ-34 blocked the hyperglycemia-induced increase in NF-{kappa}B activation in BRECs. PJ-34 also inhibited diabetes-induced increase expression of intercellular adhesion molecule-1, a product of NF-{kappa}B–dependent transcription in retina, and subsequent leukostasis. Inhibition of PARP or NF-{kappa}B inhibited the hyperglycemia (25 mmol/l glucose)-induced cell death in retinal endothelial cells. Thus, PARP activation plays an important role in the diabetes-induced death of retinal capillary cells, at least in part via its regulation of NF-{kappa}B.

Address correspondence and reprint requests to Timothy S. Kern, PhD, Professor of Medicine and Ophthalmology, 434 Biomedical Research Bldg., Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. E-mail: tsk{at}po.cwru.edu


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
R. A. Gubitosi-Klug, R. Talahalli, Y. Du, J. L. Nadler, and T. S. Kern
5-Lipoxygenase, but Not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy
Diabetes, May 1, 2008; 57(5): 1387 - 1393.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
I. G. Obrosova, O. Ilnytska, V. V. Lyzogubov, I. A. Pavlov, N. Mashtalir, J. L. Nadler, and V. R. Drel
High-Fat Diet Induced Neuropathy of Pre-Diabetes and Obesity: Effects of "Healthy" Diet and Aldose Reductase Inhibition
Diabetes, October 1, 2007; 56(10): 2598 - 2608.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. D. Shelton, T. S. Kern, and J. J. Mieyal
Glutaredoxin Regulates Nuclear Factor {kappa}-B and Intercellular Adhesion Molecule in Muller Cells: MODEL OF DIABETIC RETINOPATHY
J. Biol. Chem., April 27, 2007; 282(17): 12467 - 12474.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. Zheng, S. J. Howell, D. A. Hatala, K. Huang, and T. S. Kern
Salicylate-Based Anti-Inflammatory Drugs Inhibit the Early Lesion of Diabetic Retinopathy
Diabetes, February 1, 2007; 56(2): 337 - 345.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. S. Kern, C. M. Miller, Y. Du, L. Zheng, S. Mohr, S. L. Ball, M. Kim, J. A. Jamison, and D. P. Bingaman
Topical Administration of Nepafenac Inhibits Diabetes-Induced Retinal Microvascular Disease and Underlying Abnormalities of Retinal Metabolism and Physiology
Diabetes, February 1, 2007; 56(2): 373 - 379.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
W. Chen, D. B. Jump, W. J. Esselman, and J. V. Busik
Inhibition of Cytokine Signaling in Human Retinal Endothelial Cells through Modification of Caveolae/Lipid Rafts by Docosahexaenoic Acid
Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 18 - 26.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. Zheng, B. Gong, D. A. Hatala, and T. S. Kern
Retinal Ischemia and Reperfusion Causes Capillary Degeneration: Similarities to Diabetes
Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 361 - 367.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Szabo, A. Biser, R. Benko, E. Bottinger, and K. Susztak
Poly(ADP-Ribose) Polymerase Inhibitors Ameliorate Nephropathy of Type 2 Diabetic Leprdb/db Mice
Diabetes, November 1, 2006; 55(11): 3004 - 3012.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
H. Kaur, S. Chen, X. Xin, J. Chiu, Z. A. Khan, and S. Chakrabarti
Diabetes-Induced Extracellular Matrix Protein Expression Is Mediated by Transcription Coactivator p300
Diabetes, November 1, 2006; 55(11): 3104 - 3111.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
W. Sun, P. J. Oates, J. B. Coutcher, C. Gerhardinger, and M. Lorenzi
A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy.
Diabetes, October 1, 2006; 55(10): 2757 - 2762.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
O. Ilnytska, V. V. Lyzogubov, M. J. Stevens, V. R. Drel, N. Mashtalir, P. Pacher, M. A. Yorek, and I. G. Obrosova
Poly(ADP-Ribose) Polymerase Inhibition Alleviates Experimental Diabetic Sensory Neuropathy
Diabetes, June 1, 2006; 55(6): 1686 - 1694.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
W. Sun, C. Gerhardinger, Z. Dagher, T. Hoehn, and M. Lorenzi
Aspirin at Low-Intermediate Concentrations Protects Retinal Vessels in Experimental Diabetic Retinopathy Through Non-Platelet-Mediated Effects
Diabetes, December 1, 2005; 54(12): 3418 - 3426.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
I. G. Obrosova, V. R. Drel, P. Pacher, O. Ilnytska, Z. Q. Wang, M. J. Stevens, and M. A. Yorek
Oxidative-Nitrosative Stress and Poly(ADP-Ribose) Polymerase (PARP) Activation in Experimental Diabetic Neuropathy: The Relation Is Revisited
Diabetes, December 1, 2005; 54(12): 3435 - 3441.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
W. Chen, W. J. Esselman, D. B. Jump, and J. V. Busik
Anti-inflammatory Effect of Docosahexaenoic Acid on Cytokine-Induced Adhesion Molecule Expression in Human Retinal Vascular Endothelial Cells
Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4342 - 4347.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. Li, V. R. Drel, C. Szabo, M. J. Stevens, and I. G. Obrosova
Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy
Diabetes, May 1, 2005; 54(5): 1514 - 1522.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.