Superoxide dismutase, catalase, and glutathione peroxidase activities in copper/zinc-superoxide dismutase transgenic mice.
Copper/zinc-superoxide dismutase (CuZn-SOD) transgenic mice overexpress the gene for human CuZn-SOD. To assess the effects of the overexpression of CuZn-SOD on the brain scavenging systems, we have measured the activities of manganese-SOD (Mn-SOD), catalase, and glutathione peroxidase (GSH-Px) in various regions of the mouse brain. In nontransgenic mice, cytosolic CuZn-SOD activity was highest in the caudate-putamen complex; this was followed by the brainstem and the hippocampus. The lowest activity was observed in the cerebellum. In transgenic mice, there were significant increases of cytosolic CuZn-SOD activity in all of these regions, with ratios varying from a twofold increase in the brainstem to 3.42-fold in the cerebellum in comparison with nontransgenic mice. Particulate Mn-SOD was similarly distributed in all brain regions, and its levels also were significantly increased in superoxide dismutase (SOD)-transgenic mice. In the brains of nontransgenic mice, cytosolic catalase activity was similar in all brain regions except the cortex, which showed less than 50% of the activity observed in the other regions. In transgenic mice, cytosolic catalase activity was significantly increased, with the cortex showing the greatest changes (133%) in comparison with nontransgenic mice. The smallest increases were observed in the hippocampus (34%). In contrast to what was observed for SOD and catalase, there were no significant changes in cytosolic GSH-Px activity in any of the brain regions examined. The present results indicate that, in addition to displaying marked increases in the levels of brain CuZn-SOD activity, SOD-transgenic mice also exhibit increases in other enzymes that scavenge oxygen-based radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Przedborski
S
S
Department of Neurology, College of Physicians & Surgeons, Columbia University, New York, New York 10032.
Jackson-Lewis
V
V
Kostic
V
V
Carlson
E
E
Epstein
C J
CJ
Cadet
J L
JL
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001769:Blood / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000378:metabolism*
D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000640:Amitrole