A brain-specific isoform of apoptosis-inducing factor 2 attenuates ischemia-induced oxidative stress in HT22 cells. (January 2018)

• Record Type: Journal Article
• Authors: Xie, Yuanyang; Wanggou, Siyi; Liu, Qing; Li, Xuejun; Liu, Jingping; Wu, Ming
• Is Part Of: Neurochemistry international. Volume 112(2017)
• Page Start: 179
• Page End: 186
• Publication Date: 2018-01
• Subjects: Brain ischemia -- Apoptosis-inducing factor -- Oxygen and glucose deprivation -- Mitochondrial dysfunction; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.07.006
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Apoptosis-inducing factor (AIF) is a family of conserved mitochondrial flavoproteins that have both vital and lethal functions in cells. The function and regulation of AIF-1, the original described and most abundant isoform, has been extensively studied, whereas three other AIF isoforms have not been further characterized. Here, we investigated the role of AIF-2, a brain-specific isoform of AIF, in an in vitro ischemia model in neuronal HT22 cells. We showed that AIF-2 was constitutively expressed in HT22 cells, and the oxygen and glucose deprivation (OGD) did not alter AIF-2 expression. Downregulation of AIF-2 with specific siRNA aggravated OGD-induced lactate dehydrogenase (LDH) release, apoptosis and loss of cell viability, whereas overexpression of AIF-2 through lentivirus transfection exerted the opposite effects. In OGD-treated cells, AIF-2 overexpression promoted the endogenous antioxidant enzyme activities, preserved mitochondrial membrane potential (MMP), inhibited cytochrome c release, and thereby prevented reactive oxygen species (ROS) generation and lipid peroxidation. In addition, AIF-2 significantly prevented the OGD-induced AIF-1 translocation from cytoplasm to the nuclei. In view of these considerations, AIF-2 might represent an ideal strategy to avoid AIF-1 associated neurotoxicity, and could be tested against brain ischemia in animal models. Highlights: AIF-2 attenuates OGD-induced cytotoxicity in HT22 cells. AIF-2 suppresses OGD-induced oxidative stress. AIF-2 preserves mitochondrial function after OGD. AIF-2 prevents OGD-induced AIF-1 translocation.