Research Paper Volume 13, Issue 5 pp 6712—6723
CPI-1189 protects neuronal cells from oxygen glucose deprivation/re-oxygenation-induced oxidative injury and cell death
- 1 Department of Anesthesiology, Lianshui County People's Hospital, Lianshui, China
- 2 Anxi Maternal and Child Health Hospital, Anxi, China
- 3 Department of Anesthesiology, Affiliated Hospital of Yangzhou University, Yangzhou, China
Received: October 23, 2020 Accepted: December 23, 2020 Published: February 17, 2021
https://doi.org/10.18632/aging.202528How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces profound oxidative injury and neuronal cell death. It mimics ischemia-reperfusion neuronal injury. CPI-1189 is a novel tumor necrosis factor alpha-inhibiting compound with potential neuroprotective function. Here in SH-SY5Y neuronal cells and primary murine cortical neurons, CPI-1189 pretreatment potently inhibited OGDR-induced viability reduction and cell death. In OGDR-stimulated neuronal cells, p38 phosphorylation was blocked by CPI-1189. In addition, CPI-1189 alleviated OGDR-induced reactive oxygen species production, lipid peroxidation, and glutathione consumption. OGDR-induced neuronal cell apoptosis was also inhibited by CPI-1189 pretreatment. Furthermore, in SH-SY5Y cells and cortical neurons, CPI-1189 alleviated OGDR-induced programmed necrosis by inhibiting mitochondrial p53-cyclophilin D-adenine nucleotide translocase 1 association, mitochondrial depolarization, and lactate dehydrogenase release to the medium. In summary, CPI-1189 potently inhibited OGDR-induced oxidative injury and neuronal cell death.