title: Apobec-1 increases cyclooxygenase-2 and aggravates injury in oxygen-deprived neurogenic cells and middle cerebral artery occlusion rats.
abstract: Given that cyclooxygenase-2 (COX-2) plays a crucial role during cerebral ischemia and Apobec-1 is a critical regulator of COX-2 mRNA stabilization in gastrointestinal settings, the correlation of COX-2 and Apobec-1 was investigated in neurogenic cells and rat model of cerebral ischemia. After neurogenic SH-SY5Y, NG108-15 and PC12 cells were exposed to oxygen-glucose deprivation, cell viability, LDH leakage and Apobec-1 expression were determined. The effect of Apobec-1 overexpression on injury severity of oxygen-glucose deprivation, COX-2 expression, C-to-U editing of COX-2 mRNA were measured in vitro. Then the correlation of Apobec-1 level and injury severity was analyzed in cells with oxygen-glucose deprivation and in rats with middle cerebral artery occlusion. Apobec-1 expression was elevated along with upregulation of COX-2 and injury severity of oxygen-glucose deprivation in the three cell lines. Apobec-1 overexpression aggravated injury of oxygen-glucose deprivation in vitro and could be correlated to injury severity in vivo. Meanwhile, Apobec-1 increased COX-2 expression and COX-2 mRNA stabilization in neurogenic cells, and failed to catalyze C-to-U editing of COX-2 mRNA. Apobec-1 could upregulate COX-2 expression in neurogenic cells by stabilizing COX-2 mRNA, and might aggravate injury of oxygen-glucose deprivation in neurogenic cells as well as in rats with cerebral ischemia.
authors.affiliation: Department of Neurology, First Affiliated Hospital, China Medical University, North Nanjing Street #155, Shenyang, Liaoning Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Hui-sheng
authors.initials: HS
authors.lastname: Chen
authors.forename: Zhi-yi
authors.initials: ZY
authors.lastname: He
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D001483:Base Sequence; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D003564:Cytidine Deaminase / Q000502:physiology*; D017931:DNA Primers; D004790:Enzyme Induction; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D017393:RNA Editing; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D045442:Rotarod Performance Test
chemical_list: D017931:DNA Primers; D051546:Cyclooxygenase 2; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase; D005947:Glucose