Tang-Luo-Ning, a Traditional Chinese Medicine, Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis of Schwann Cells under High Glucose Environment.

Weijie Yao,Liping Xu,Biane Gao,Xinwei Yang,Jiayue Zhu,Renhui Liu

doi:10.1155/2017/5193548

Abstract

Tang-Luo-Ning (TLN) has a definite effect in the clinical treatment of diabetic peripheral neuropathy (DPN). Schwann cells (SCs) apoptosis induced by endoplasmic reticulum stress (ER stress) is one of the main pathogeneses of DPN. This study investigates whether TLN can inhibit SCs apoptosis by inhibiting ER stress-induced apoptosis. Our previous researches have demonstrated that TLN could increase the expression of ER stress marker protein GRP78 and inhibited the expression of apoptosis marker protein CHOP in ER stress. In this study, the results showed that TLN attenuated apoptosis by decreasing Ca2+ level in SCs and maintaining ER morphology. TLN could decrease downstream proteins of CHOP including GADD34 and Ero1α, while it increased P-eIF2α and decreased the upstream proteins of CHOP including P-IRE1α/IRE1α and XBP-1, thereby reducing ER stress-induced apoptosis.

Highlights

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes [1] and its pathogenesis is complex
Results showed that Ca2+ level in 150 mM glucose group increased significantly compared with 25 mM group (P < 0.01), and TLN serum decreased Ca2+ level significantly (P < 0.01), alleviating high glucoseinduced apoptosis (Figure 2)
We found that the expressions of P-IRE1α/IRE1α and XBP-1 in 150 mM glucose group increased significantly compared with the 25 mM glucose group (P < 0.05 and P < 0.01) (Figures 5(c)–5(f)); they showed the same trend compared with the expression of CHOP

Summary

Introduction

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes [1] and its pathogenesis is complex. Schwann cells (SCs) apoptosis induced by hyperglycemia is involved in the pathogenesis of DPN [2]. SCs apoptosis induced by hyperglycemia is a key factor in decreasing nerve conduction velocity and increasing thermal perception threshold, axon atrophy, and demyelination of DPN [4, 5]. Recent studies have shown that endoplasmic reticulum stress- (ER stress-) induced apoptosis is involved in the pathogenesis of DPN [6, 7]. ER stress results from the accumulation of unfolded proteins or misfolded proteins in the ER. Persistent ER stress can induce apoptosis [8].

Objectives

Methods

Results

Conclusion