Expression of human A4V mutant Cu,Zn superoxide dismutase in Schizosaccharomyces pombe: investigations of its toxic properties.
Cu,Zn superoxide dismutase (SOD1) is an antioxidant enzyme that catalyzes the removal of superoxide radicals generated in various biological oxidations. Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative disorders, occurring in families (FALS) and sporadically (SALS). FALS and SALS are distinguishable genetically but not clinically. More than 100 point mutations in the human SOD 1 gene have been identified that cause FALS. In order to determine the effects of mutant SOD protein, we first cloned wild-type and A4V mutant human SOD1 into Schizosaccharomyces pombe. This study shows viabilities and some antioxidant properties including SOD, catalase, proteasomal activity, and protein carbonyl levels of transformants in SOD1 deleted strain (MN415); and its parental strain (JY741) at different stress conditions. There was no more oxidative damage in the human mutant SOD carrying the transformant strain compared with other strains. These results may help to explain whether ALS progresses as a consequence of cellular oxidative damage.
Karaer
Semian
S
Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey.
Tarhan
Cagatay
C
Pekmez
Murat
M
Hamad
Ismail
I
Arda
Nazli
N
Sarikaya
Aysegul Topal
AT
D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival; D003001:Cloning, Molecular / Q000379:methods; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D007700:Kinetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D002374:Catalase; D013482:Superoxide Dismutase; D046988:Proteasome Endopeptidase Complex