RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

A novel type of programmed necrosis called necroptosis has been identified in the field of cell death, thereby offering an opportunity for re-examining necrosis after spinal cord injury (SCI). Several recent studies have suggested receptor-interacting protein kinase 3 (RIP3) plays an important role in necrosis in many cell types. However, it is still unclear what downstream events that lead to cell death are triggered by RIP3 activation. Hence, link between RIP3 inhibition and induction of neuronal cell death via mitochondrial function and antioxidative capacity after SCI was studied in our work. We examined the protective effects of RIP3 inhibition in SCI-mice. Furthermore, mimicking the pathological conditions of SCI in vitro, spinal cord neurons were subjected to oxygen-glucose deprivation. Notably, we found GSK872 and Nec-1 ameliorated the locomotor function and spinal cord edema, and conferred reverse of SCI-induced loss of mitochondrial integrity, ATP, glutathione and superoxide dismutase and elevation of reactive oxygen species and malonyldialdehyde in SCI-mice. Moreover, GSK872alleviated OGD-inducted mitochondrial dysfunction, decreased antioxidative capacity and cell death in spinal cord neurons, through inhibiting RIP3 activity. The data suggest improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention.

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Cat.No. Product Name Information Publications Customer Product Validation
S8465 GSK'872 (GSK2399872A) GSK'872 (GSK2399872A) is a potent and selective RIP3 kinase inhibitor which binds RIP3 kinase domain with high affinity (IC50=1.8 nM) and inhibits kinase activity with IC50 of 1.3 nM. It has minimal cross-reactivity. (42) (1)

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