Coenzyme Q10 Regulation of Apoptosis and Oxidative Stress in H2O2 Induced BMSC Death by Modulating the Nrf-2/NQO-1 Signaling Pathway and Its Application in a Model of Spinal Cord Injury.

Xing Li,Le Wang,Yu Hou,Yonghui Hou,Jiyao Luan,Dingkun Lin,Dan Luo,Jiheng Zhan,Shudong Chen

doi:10.1155/2019/6493081

Abstract

Spinal cord injury (SCI) has always been considered to be a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patient. Stem cell-based therapy, especially using bone marrow mesenchymal stem cells (BMSCs), is a promising strategy for the treatment of SCI. However, SCI results in low rates of cell survival and a poor microenvironment, which limits the therapeutic efficiency of BMSC transplantation. Coenzyme Q10 (CoQ10) is known as a powerful antioxidant, which inhibits lipid peroxidation and scavenges free radicals, and its combined effect with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells, as well as antioxidant and antiapoptotic compounds in SCI. Therefore, we aimed to evaluate whether CoQ10 could decrease oxidative stress against the apoptosis of BMSCs in vitro and explored its molecular mechanisms. Furthermore, we investigated the protective effect of CoQ10 combined with BMSCs transplanted into a SCI model to verify its ability. Our results demonstrate that CoQ10 treatment significantly decreases the expression of the proapoptotic proteins Bax and Caspase-3, as shown through TUNEL-positive staining and the products of oxidative stress (ROS), while increasing the expression of the antiapoptotic protein Bcl-2 and the products of antioxidation, such as glutathione (GSH), against apoptosis and oxidative stress, in a H2O2-induced model. We also identified consistent results from the CoQ10 treatment of BMSCs transplanted into SCI rats in vivo. Moreover, the Nrf-2 signaling pathway was also investigated in order to detail its molecular mechanism, and the results show that it plays an important role, both in vitro and in vivo. Thus, CoQ10 exerts an antiapoptotic and antioxidant effect, as well as improves the microenvironment in vitro and in vivo. It may also protect BMSCs from oxidative stress and enhance their therapeutic efficiency when transplanted for SCI treatment.

Highlights

Spinal cord injury (SCI) has always been considered as a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patients
A large number of studies have already proven that treatment with bone marrow mesenchymal stem cells (BMSCs), which have an ability to differentiate into the neuronal-like cells, is an effective therapy for SCI [23, 33,34,35]
The survival rate of BMSCs after transplantation is low, as a result of the poor microenvironment produced in SCI, which limits its therapeutic efficiency

Summary

Introduction

Spinal cord injury (SCI) has always been considered as a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patients. It affects the physical and mental health of patients but is an economic burden on the family [1,2,3]. Methods that can be used to decrease oxidative stress, reduce apoptosis, and increase the vitality of the transplanted BMSCs are important factors that need to be researched in order to develop efficient treatment strategies for SCI [16]

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Methods

Conclusion