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K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells From Oxygen Glucose Deprivation/Re-Oxygenation

Hua Liu, Zhiqing Zhang, Min Xu, Rong Xu, Zhichun Wang, Guangfu Di

Cell Physiol Biochem. 2018;51(4):1908-1920.

PMID: 30504702

Abstract:

Background/aims:
New strategies are required to combat neuronal ischemia-reperfusion injuries. K6PC-5 is a novel sphingosine kinase 1 (SphK1) activator whose potential activity in neuronal cells has not yet been tested.
Methods:
Cell survival and necrosis were assessed with a Cell Counting Kit-8 assay and lactate dehydrogenase release assay, respectively. Mitochondrial depolarization was tested by a JC-1 dye assay. Expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling components were examined by quantitative real-timePCR and western blotting.
Results:
K6PC-5 protected SH-SY5Y neuronal cells and primary murine hippocampal neurons from oxygen glucose deprivation/re-oxygenation (OGDR). K6PC-5 activated SphK1, and SphK1 knockdown by targeted short hairpin RNA (shRNA) almost completely abolished K6PC-5-induced neuronal cell protection. Further work showed that K6PC-5 inhibited OGDR-induced programmed necrosis in neuronal cells. Importantly, K6PC-5 activated Nrf2 signaling, which is downstream of SphK1. Silencing of Nrf2 by targeted shRNA almost completely nullified K6PC-5-mediated neuronal cell protection against OGDR.
Conclusion:
K6PC-5 activates SphK1-Nrf2 signaling to protect neuronal cells from OGDR. K6PC-5 might be a promising neuroprotective strategy for ischemia-reperfusion injuries.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP756875511 K6PC-5 K6PC-5 756875-51-1 Price
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