PARK7 enhances antioxidative-stress processes of BMSCs via the ERK1/2 pathway.
PARK7 enhances antioxidative-stress processes of BMSCs via the ERK1/2 pathway.
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PARK7通过ERK1/2途径增强骨髓间充质干细胞的抗氧化应激过程。
DOI：
10.1002/jcb.29845
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发表时间：
2021-03
影响因子：
4
通讯作者：
Yan Y
中科院分区：
文献类型：
--
作者：
Zhang F;Peng W;Zhang J;Wang L;Dong W;Zheng Y;Wang Z;Xie Z;Wang T;Wang C;Yan Y
病变周围微环境中的氧化应激可诱导移植的骨髓间充质干细胞(BMSCs)凋亡。因此，迫切需要改善移植的BMSCs的抗氧化应激过程，以进一步促进其存活。本研究报道了帕金森氏病蛋白7(Park7)在增强BMSCs抗氧化活性中的作用和机制。我们用Park7慢病毒转染BMSCs，上调或下调Park7的表达，然后用过氧化氢模拟体外培养的BMSCs的氧化应激。Park7过表达可有效降低BMSCs的氧自由基和丙二醛含量，保护线粒体膜电位，对抗氧化应激诱导的BMSCs凋亡，但Park7表达下调，上述结果正好相反。同时，我们还发现，Park7的过表达增加了细胞外调节蛋白激酶1/2(ERK1/2)的磷酸化和核转位，上调了ELK1的磷酸化和超氧化物歧化酶(SOD)的表达。相反，当U0126阻断ERK1/2通路时，ERK1/2和ELK1的磷酸化水平下调，ERK1/2核转位和SOD含量显著减少，Park7过度表达诱导的抗氧化活性完全被阻断。总之，我们的结果表明，Park7过表达通过激活ERK1/2信号通路，增加了过氧化氢下BMSCs的抗氧化应激过程和存活率。我们的发现可能会指导针对Park7的策略的开发，以提高BMSCs的移植效率。帕金森病蛋白7(Park7)促进MEK1/2和细胞外调节蛋白激酶1/2(ERK1/2)的磷酸化。然后，磷酸化的ERK1/2被转移到细胞核，后者磷酸化下游的效应物ELK1。然后，磷酸化的ELK1促进抗氧化酶的表达，如超氧化物歧化酶(SOD)。抗氧化蛋白，如Park7和SOD，然后消除细胞内过量的活性氧，从而促进BMSCs在氧化应激条件下的存活。
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 H2O2 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 H2O2 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. 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.
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影响因子：
3.6
作者：
Liguori I;Russo G;Curcio F;Bulli G;Aran L;Della-Morte D;Gargiulo G;Testa G;Cacciatore F;Bonaduce D;Abete P
通讯作者：
Abete P
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
影响因子：
12.8
作者：
Jeong HJ;Kim DW;Kim MJ;Woo SJ;Kim HR;Kim SM;Jo HS;Hwang HS;Kim DS;Cho SW;Won MH;Han KH;Park JS;Eum WS;Choi SY
通讯作者：
Choi SY
影响因子：
11.1
作者：
Korolchuk VI;Miwa S;Carroll B;von Zglinicki T
通讯作者：
von Zglinicki T
影响因子：
2.7
作者：
Wang, Tiansheng;Teng, Shoufa;Guo, Li
通讯作者：
Guo, Li