title: Raf kinase inhibitor protein regulates oxygen-glucose deprivation-induced PC12 cells apoptosis through the NF-κB and ERK pathways.
abstract: Raf-1 kinase inhibitory protein (RKIP) is a critical molecule for cellular responses to stimuli. In this study, we investigated whether RKIP is responsible for neural cell apoptosis induced by oxygen-glucose deprivation (OGD) and explored the role of NF-κB and ERK pathways regulated by RKIP under OGD stimuli. RKIP was overexpressed or knocked down using lentivirus in PC12 cells, which were then challenged by OGD. RKIP overexpression significantly increased the cell viability of OGD cells, and attenuated apoptosis, cell cycle arrest, and reactive oxygen species generation. RKIP knockdown induced reverse effects. Moreover, we found that RKIP interacted with TAK1, NIK, IKK, and Raf-1 and negatively regulated the NF-κB and ERK pathways. RKIP overexpression significantly inhibited IKK, IκBα, and P65 phosphorylation in NF-κB pathway and MEK, ERK, and CREB phosphorylation in ERK pathway, respectively. RKIP knockdown induced reverse effects. Furthermore, a NF-κB inhibitor BAY 11-7082 and a MEK inhibitor U0126 blocked the changes caused by RKIP down-regulation after OGD. In conclusion, these results demonstrate that RKIP plays a key role in neural cell apoptosis caused by OGD partly via regulating NF-κB and ERK pathways. The present study may provide new insights into the role of RKIP in ischemic stroke.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, China.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Du
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, China.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Lou
keywords: ERK pathway; NF-κB pathway; OGD; PC12 cells; RKIP