Increased gene expression of antioxidant enzymes in KKAy diabetic mice but not in STZ diabetic mice.
Oxidative stress and the gene expression at the transcriptional level of antioxidant enzymes were investigated in two models of diabetes in mice. We used KKAy mice as a model of obese insulin-resistant diabetes, and streptozotocin-induced diabetic mice (STZ mice) as a model of insulin-deficient diabetes. C57BL mice and saline-injected ICR mice were used as the respective non-diabetic controls. To assess oxidative damage, plasma malonedialdehyde (MDA), urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The mRNA expression of antioxidant enzymes, superoxide dismutase 1 (SOD-1) and glutathione peroxidase 1 (GPx-1) in the kidney and heart were quantified using a real-time polymerase chain reaction. The KKAy mice demonstrated moderate hyperglycemia and hyperlipidemia, and the STZ mice showed severe hyperglycemia and hypolipidemia. The KKAy mice, but not the STZ mice, showed elevated plasma MDA relative to the non-diabetic controls. Urine 8-isoprostane and 8-OHdG in both diabetic mouse groups increased significantly. The urine oxidative stress markers in the severely hyperglycemic STZ mice were higher than those in the moderately hyperglycemic KKAy mice. Although GPx-1 and SOD-1 showed elevated mRNA expression in the KKAy mice in the kidney and heart, in the STZ mice they did not increase compared to the controls. The compensatory up-regulation of the mRNA expression of antioxidant enzymes may be impaired in the insulin-deficient severely hyperglycemic state.
Fujita
Atsuyo
A
The First department of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama, P.O. 641-8509, Japan.
Sasaki
Hideyuki
H
Ogawa
Kenichi
K
Okamoto
Kunihisa
K
Matsuno
Shohei
S
Matsumoto
Eisaku
E
Furuta
Hiroto
H
Nishi
Masahiro
M
Nakao
Taisei
T
Tsuno
Takuo
T
Taniguchi
Hisaji
H
Nanjo
Kishio
K
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D048909:Diabetes Complications / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000235:genetics*; D007333:Insulin Resistance; D007668:Kidney / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000201:enzymology; D009765:Obesity; D013482:Superoxide Dismutase / Q000235:genetics*
D017931:DNA Primers; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase