Genotype effects on the antioxidant enzymes activity and mRNA expression in liver and kidney tissues of autoimmune-prone MRL/MpJ-lpr/lpr mice.
Congeneic pairs of MRL/lpr and MRL/++ (+/+) mice differ in incidence of autoantibodies, lymphoproliferative disease and survival, characteristics that are linked to immunological abnormalities. MRL/lpr mice have a significantly shorter life span compared to +/+ mice. Because a weak antioxidant defense and an increased generation of free radicals are generally implicated in the severity of many autoimmune disease, the present study was undertaken to compare the influence of genotype on lipid composition, lipid peroxidation and expression of mRNA, and activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in the livers and kidneys of these mice. The expression of SOD, GSH-Px and CAT mRNAs was significantly higher (P < 0.05) in the livers of +/+ mice, while in the kidneys only SOD expression was found significantly higher in +/+ mice when compared to MRL/lpr mice. Further, the activity of cytosolic SOD and GSH-Px was also found significantly higher (P < 0.001) in the livers of +/+ mice. Both livers and kidneys of MRL/lpr mice exhibited significantly higher levels of arachidonic acid (20:4(n-6)), significantly higher generation of thiobarbituric acid reactive substances (TBARS) and higher estimated peroxidation index than the +/+ mice. In addition, the MRL/lpr mice had higher levels of serum anti-cardiolipin antibodies. In summary, the results from the present study indicate that besides several immune-related abnormalities, the MRL/lpr mice may exhibit their inability to cope with oxidative stress due to a poor antioxidant defense system.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.
J T
JT
Venkatraman
B
B
Chandrasekar
J D
JD
Kim
G
G
Fernandes
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000975:Antioxidants / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism; D001835:Body Weight; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D066298:In Vitro Techniques; D007668:Kidney / Q000737:chemistry / Q000201:enzymology*; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis*
D017153:Antibodies, Anticardiolipin; D000975:Antioxidants; D005227:Fatty Acids; D012333:RNA, Messenger