Int J Med Sci 2022; 19(13):1965-1976. doi:10.7150/ijms.69992 This issue Cite

Research Paper

Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in Rat Schwann cells

Baoli Wang1,2,3#, Jiayao Fu1,2,3,4,5#, Ying Chai1,2,3, Yuemin Liu1,2,3,4, Yanlin Chen5,6, Junhao Yin1,2,3,4,5, Yiping Pu1,2,3, Changyu Chen1,2,3,4,5, Fang Wang1,2,3, Zhiyang Liu1,2,3, Lingyan Zheng1,2,3,4✉, Minjie Chen1,2,3,4✉

1. Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. National Center for Stomatology, Shanghai, China.
3. National Clinical Research Center of Oral Disease, Shanghai, China.
4. Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
5. Laboratory of oral microbiota and systematic diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
6. Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
#Baoli Wang and Jiayao Fu contribute equally to this work

Citation:
Wang B, Fu J, Chai Y, Liu Y, Chen Y, Yin J, Pu Y, Chen C, Wang F, Liu Z, Zheng L, Chen M. Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in Rat Schwann cells. Int J Med Sci 2022; 19(13):1965-1976. doi:10.7150/ijms.69992. https://www.medsci.org/v19p1965.htm
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Abstract

Graphic abstract

The injury of Schwann cells is an important pathological feature of peripheral neuropathy. However, the explicit molecular mechanism and blocking method remains to be explored. In this study, we identified an pivotal executor of necroptosis—RIPK1, performed an unique function in response to oxidative stress-induced injury in Rat Schwann cells. We found that after oxidative stress-simulation by H2O2, RIPK1 was activated independent of genetic up-regulation, but through the post-translational modification, including its protein levels, phosphorylation of Serine 166 and Serine 321 sites and its general ubiquitination levels. Under a confocal microscopy, we found that RIPK1 was significantly accumulated into the mitochondria. And the phosphorylation, ubiquitination levels were also elevated in mitochondrial RIPK1, as indicated by immunoprecipitation. Through the administration of N-Acetyl-L-cysteine (NAC), a ROS inhibitor, we found that the phosphorylation, ubiquitination and mitochondrial location of RIPK1 was significantly suppressed. While administration of Necrostatin-1 (Nec-1) failed to influence the levels of ROS and mitochondrial membrane potential, revealing that RIPK1 served as the down-stream regulators of ROS. Lastly, pharmacological inhibition of RIPK1 by Nec-1 attenuated the levels of necroptosis, increased proliferation, as indicated by Annexin V/PI evaluation, CCK-8 detection, TEM scanning and EdU staining. Our results indicate a previous un-recognized post-translational change of RIPK1 in response to oxidative stress in Schwann cells.

Keywords: Oxidative stress, RIPK1, Schwann cells, necroptosis, Reactive Oxygen Species


Citation styles

APA
Wang, B., Fu, J., Chai, Y., Liu, Y., Chen, Y., Yin, J., Pu, Y., Chen, C., Wang, F., Liu, Z., Zheng, L., Chen, M. (2022). Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in Rat Schwann cells. International Journal of Medical Sciences, 19(13), 1965-1976. https://doi.org/10.7150/ijms.69992.

ACS
Wang, B.; Fu, J.; Chai, Y.; Liu, Y.; Chen, Y.; Yin, J.; Pu, Y.; Chen, C.; Wang, F.; Liu, Z.; Zheng, L.; Chen, M. Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in Rat Schwann cells. Int. J. Med. Sci. 2022, 19 (13), 1965-1976. DOI: 10.7150/ijms.69992.

NLM
Wang B, Fu J, Chai Y, Liu Y, Chen Y, Yin J, Pu Y, Chen C, Wang F, Liu Z, Zheng L, Chen M. Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in Rat Schwann cells. Int J Med Sci 2022; 19(13):1965-1976. doi:10.7150/ijms.69992. https://www.medsci.org/v19p1965.htm

CSE
Wang B, Fu J, Chai Y, Liu Y, Chen Y, Yin J, Pu Y, Chen C, Wang F, Liu Z, Zheng L, Chen M. 2022. Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in Rat Schwann cells. Int J Med Sci. 19(13):1965-1976.

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