RIP1 mediates the protection of geldanamycin on neuronal injury induced by oxygen-glucose deprivation combined with zVAD in primary cortical neurons |
| |
Authors: | Chen Wei-Wei Yu Hailong Fan Hong-Bin Zhang Cui-Cui Zhang Min Zhang Caiyi Cheng Yanbo Kong Jiming Liu Chun-Feng Geng Deqin Xu Xingshun |
| |
Institution: | Department of Neurology, Xuzhou Medical College Affiliated Hospital, Xuzhou, Jiangsu Province, China. |
| |
Abstract: | Caspase-dependent apoptosis is considered one of the most important cell death pathways. When the apoptotic process is blocked, a form of programmed necrosis called necroptosis occurs. Apoptosis and necroptosis may share some regulatory mechanisms. Recent studies indicated that receptor interacting protein 1 (RIP1), an Hsp90-associated kinase, is an important regulatory switch between apoptosis and necroptosis. In this study, we showed that oxygen-glucose deprivation (OGD) combined with a caspase inhibitor zVAD (OGD/zVAD)-induced RIP1 protein expression in a time-dependent manner. We found that geldanamycin (GA), a benzoquinone ansamycin, protected against neuronal injury induced by OGD/zVAD treatment in cultured primary neurons. More importantly, GA decreased RIP1 protein level in a time- and concentration-dependent manner. In this study, we found that GA also decreased the Hsp90 protein level, which caused instability of RIP1 protein, resulting in decreased RIP1 protein level but not RIP1 mRNA level after GA treatment. We concluded that the GA-mediated protection against OGD/zVAD-induced neuronal injury was associated with enhanced RIP1 protein instability by decreasing Hsp90 protein level. GA and its derivatives may be promising for the prevention of neuronal injury during ischemic injury. |
| |
Keywords: | geldanamycin Hsp90 necroptosis oxygen‐glucose deprivation RIP1 |
本文献已被 PubMed 等数据库收录! |
|