MODULATION OF OXYGEN-RADICAL-SCAVENGING ENZYMES BY OXIDATIVE STRESS IN PRIMARY CULTURES OF RAT ASTROGLIAL CELLS

Cytosolic and mitochondrial alterations induced by exposure of rat ast roglial primary cultures to reactive oxygen species (ROS) generated by a xanthine/xanthine oxidase (X/XO) mixture or by lipopolysaccharide ( LPS) have been investigated biochemically and immunochemically. In the presence of ROS generated by X/XO, a significant decrease in Cu,Zn su peroxide dismutase (Cu,Zn-SOD) and in glutamine synthetase (GS) activi ty was observed whereas mitochondrial Mn-SOD activity and enzyme prote in levels were significantly enhanced. Similar effects on GS, Cu,Zn- a nd Mn-SOD activities were observed by glucose/glucose oxidase treatmen t of the cells. Addition of LPS to the cell growth medium also specifi cally induces Mn-SOD synthesis but was without effect on Cu,Zn-SOD. It is suggested that in all these tested situations, hydrogen peroxide c ould represent a specific inducer of the observed phenomenon and it ma y therefore be considered as an intracellular messenger involved in th e regulation of some aspects of astroglial oxidative metabolism, parti cularly the defence against ROS.