CGRP Reduces Apoptosis of DRG Cells Induced by High-Glucose Oxidative Stress Injury through PI3K/AKT Induction of Heme Oxygenase-1 and Nrf-2 Expression.

Yadong Liu,Sicong Zhang,Ping Ao,Liucheng Ding,Baixin Shen,Jun Xue,Zhongqing Wei

doi:10.1155/2019/2053149

Abstract

Dorsal root ganglion (DRG) neurons, which are sensitive to oxidative stress due to their anatomical and structural characteristics, play a complex role in the initiation and progression of diabetic bladder neuropathy. We investigated the hypothesis that the antioxidant and antiapoptotic effects of CGRP may be partly related to the expression of Nrf2 and HO-1, via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, thus reducing apoptosis and oxidative stress responses. This study shows that CGRP activates the PI3K/AKT pathway, thereby inducing increased expression of Nrf2 and HO-1 and resulting in the decrease of reactive oxygen species and malondialdehyde levels and reduced neuronal apoptosis. These effects were suppressed by LY294002, an inhibitor of the PI3K/AKT pathway. Therefore, regulation of Nrf2 and HO-1 expression by the PI3K/AKT pathway plays an important role in the regulation of the antioxidant and antiapoptotic responses in DRG cells in a high-glucose culture model.

Highlights

The prevalence of diabetes mellitus (DM) has significantly increased worldwide, accompanied by an increase in the incidence of obesity
At the indicated glucose concentration, the cell viability of Dorsal root ganglion (DRG) cells in the HG+Calcitonin gene-related peptide (CGRP) group was significantly improved compared to the HG group (p < 0:01)
We have evaluated the effects of CGRP on antioxidation and antiapoptosis in a high-glucose culture model of DRG cells

Summary

Introduction

The prevalence of diabetes mellitus (DM) has significantly increased worldwide, accompanied by an increase in the incidence of obesity. The molecular mechanism leading to DCP in neuronal dysfunction remains largely unclear, accumulating evidence shows that it is related to oxidative stress injury [5,6,7]. This has been confirmed by previous studies in diabetic rats treated with antioxidants [8, 9]. Some studies have reported a close relationship between diabetesinduced peripheral neuropathy and bladder dysfunction [10] This has been further confirmed by neuromodulation in the treatment of voiding dysfunction in diabetic rats [11]

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