Apobec-1 increases cyclooxygenase-2 and aggravates injury in oxygen-deprived neurogenic cells and middle cerebral artery occlusion rats

Neurochem Res. 2013 Jul;38(7):1434-45. doi: 10.1007/s11064-013-1043-y. Epub 2013 Apr 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-1 Deaminase
  • Animals
  • Base Sequence
  • Cell Hypoxia*
  • Cell Line, Tumor
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • Cytidine Deaminase / physiology*
  • DNA Primers
  • Enzyme Induction
  • Glucose / metabolism
  • Humans
  • Infarction, Middle Cerebral Artery / enzymology
  • Infarction, Middle Cerebral Artery / metabolism*
  • Male
  • Neurons / metabolism*
  • RNA Editing
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Rotarod Performance Test

Substances

  • DNA Primers
  • Cyclooxygenase 2
  • APOBEC-1 Deaminase
  • APOBEC1 protein, human
  • Apobec1 protein, rat
  • Cytidine Deaminase
  • Glucose