Effects of proteasome inhibitor MG132 nuclear factor-kappa B pathway and retinal ganglion cells apoptosis in rats with diabetic retinopathy

Abstract

Objective To observe the degradation regulation of ubiquitin-proteasome inhibitor nuclear factor κB(NF-κB)and its inhibitory signal protein IκB kinase in earlier period diabetic retinopathy(DR), and the effects on retinal ganglion cells (RGC) apoptosis. Methods Forty healthy adult Wistar rats were randomly divided into control (group A), DR(group B), DR+low-concentration MG132-treated (group C) and DR+high-concentration MG132-treated(group D)groups, 10 rats in each group. After 6 and 8 weeks, the results of body masses and fasting blood glucose (FBG) were detected, the expression of NF-κB and IκB were observed by immunohistoehemistry respectively. RGC apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method. Results The expression of NF-κB was up-regulated in group B compared with group A, its expression decreased in group D compared with group B; but the expression of IκB was contrary to NF-κB; RGC apoptosis was followed a similar pattern with the expression of NF-κB; the differences among them were statistically significant (P 0. 05). Conclusion Ubiquitin-proteasome inhibitor MG132 can block the activation of NF-κB, inhibit ubiquitination of IκB degradation and RGC apoptosis. Key words: Diabetic retinopathy/Phisiopathology; NF-kappa B; Ubiquitin-protein ligases/antagonists inhibitors; Retinal ganglion cells/physiology; Apoptosis/drug effects; Diabetes mellitus, experimental