PARK7 enhances antioxidative‐stress processes of BMSCs via the ERK1/2 pathway. Issue 2 (12th September 2020)

• Record Type: Journal Article
• Authors: Zhang, Fei; Peng, Wuxun; Zhang, Jian; Wang, Lei; Dong, Wentao; Zheng, Yinggang; Wang, Zhenwen; Xie, Zhihong; Wang, Tao; Wang, Chuan; Yan, Yanglin
• Is Part Of: Journal of cellular biochemistry. Volume 122:Issue 2(2021)
• Page Start: 222
• Page End: 234
• Publication Date: 2020-09-12
• Subjects: bone‐marrow‐derived mesenchymal stem cells -- extracellular‐regulated protein kinase 1/2 -- oxidative stress -- Parkinson's disease protein 7; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29845
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Oxidative stresss in the microenvironment surrounding lesions induces apoptosis of transplanted bone‐marrow‐derived mesenchymal stem cells (BMSCs). Hence, there is an urgent need for improving antioxidative‐stress processes of transplanted BMSCs to further promote their survival. The present study reports the role and mechanism of Parkinson's disease protein 7 (PARK7) in enhancing antioxidative activity in BMSCs. We used a PARK7 lentivirus to transfect BMSCs to up‐ or downregulate PARK7, and then used H2 O2 to simulate oxidative stress in BMSCs in vitro. Overexpression of PARK7 effectively reduced reactive oxygen species and malondialdehyde, protected mitochondrial membrane potential, and resisted oxidative‐stress‐induced apoptosis of BMSCs, but the expression of PARK7 was downregulated, these results were reversed. At the same time, we also found that overexpression of PARK7 increased extracellular‐regulated protein kinase 1/2 (ERK1/2) phosphorylation and nuclear translocation, as well as upregulated Elk1 phosphorylation and superoxide dismutase (SOD) expression. In contrast, when U0126 was used to block the ERK1/2 pathway, ERK1/2 and Elk1 phosphorylation levels were downregulated, ERK1/2 nuclear translocation and SOD content were significantly reduced, and PARK7‐overexperssion‐induced antioxidative activity was completely blocked. Collectively, our results suggest that PARK7 overexpression increased antioxidative‐stress processes and survival of BMSCs subjected to H2 O2 via activating the ERK1/2 signaling pathway. Our findings may guide the development of a PARK7‐specific strategy for improving the transplantation efficacy of BMSCs. Abstract : Parkinson's disease protein 7 (PARK7) promotes the phosphorylation of MEK1/2 and extracellular‐regulated protein kinase 1/2 (ERK1/2). Phosphorylated ERK1/2 is then transferred to the nucleus, which phosphorylates the downstream effector, Elk1. Phosphorylated Elk1 then promotes the expression of antioxidative enzymes, such as superoxide dismutase (SOD). Antioxidative proteins, such as PARK7 and SOD, then eliminate excessive intracellular reactive oxygen species (ROS), thereby promoting the survival of BMSCs under oxidative‐stress conditions.