Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-κB

Ling Zheng, Csaba Szabó, Timothy S. Kern

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    197 Scopus citations

    Abstract

    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-κB (NF-κB) in the retinal cells. In bovine retinal endothelial cells (BRECs), PARP interacted directly with both subunits of NF-κB (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-κB activation in BRECs. PJ-34 also inhibited diabetes-induced increase expression of intercellular adhesion molecule-1, a product of NF-κB-dependent transcription in retina, and subsequent leukostasis. Inhibition of PARP or NF-κB 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-κB.

    Original languageEnglish (US)
    Pages (from-to)2960-2967
    Number of pages8
    JournalDiabetes
    Volume53
    Issue number11
    DOIs
    StatePublished - Nov 1 2004

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    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

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