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The Poly(ADP-Ribose)Polymerase-1 Inhibitor 1,5-Isoquinolinediol Attenuate Diabetes-Induced NADPH Oxidase-Derived Oxidative Stress in Retina

The Poly(ADP-Ribose)Polymerase-1 Inhibitor 1,5-Isoquinolinediol Attenuate Diabetes-Induced NADPH Oxidase-Derived Oxidative Stress in Retina

Ghulam Mohammad, Saleh Hamed Alrashed, Abdullah Ibrahim Almater, Mohammad Mairaj Siddiquei, Ahmed M Abu El-Asrar

J Ocul Pharmacol Ther. 2018 Sep;34(7):512-520.

PMID: 29912609

Abstract:

Purpose:
To examine the effects of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitor 1,5-isoquinolinediol (IQ) on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived oxidative stress in diabetic retina.
Methods:
Streptozotocin-induced diabetic rats were treated with IQ. The NADPH oxidase enzyme activity was determined by luminometer. Expression of gp91phox, P47phox and nitrated proteins was examined by western blot. Interaction between gp91phox and P47phox was determined by coimmunoprecipitation. Enzyme-linked immunosorbent assay was utilized to measure the level of retinal total antioxidant capacity. We also studied the effect of the IQ on hydrogen peroxide (H2O2)-induced cleavage of PARP-1 and caspase-3 in human retinal Müller glial cells.
Results:
Treatment of retinal Müller cells with H2O2-induced PARP-1 and caspase-3 cleavage that was attenuated by IQ cotreatment. Diabetes upregulated PARP-1, NADPH oxidase enzyme activity, gp91phox, P47phox, nitrated protein expression and interaction between gp91phox and P47phox, and downregulated total antioxidant capacity in the retinas compared with nondiabetic rats. Administration of IQ did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of NADPH oxidase enzyme activity and expressions of gp91phox, P47phox, and nitrated proteins and interaction between gp91phox and P47phox. In addition, IQ ameliorated diabetes-induced downregulation of total antioxidant capacity in the retina.
Conclusion:
PARP-1 inhibition by IQ protects diabetic retina from NADPH oxidase-derived oxidative stress. Thus, inhibition of PARP-1 could have potential therapeutic value in preventing the development of diabetic retinopathy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP5154029-A	1,5-Isoquinolinediol		5154-02-9	Price

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