title: Therapeutic effect of MG132 on the aortic oxidative damage and inflammatory response in OVE26 type 1 diabetic mice.
abstract: The present study tested whether MG132 increases vascular nuclear factor E2-related factor-2 (Nrf2) expression and transcription to provide a therapeutic effect on diabetes-induced pathogenic changes in the aorta. To this end, three-month-old OVE26 diabetic and age-matched control mice were intraperitoneally injected with MG-132, 10  μ g/kg daily for 3 months. OVE26 transgenic type 1 diabetic mice develop hyperglycemia at 2-3 weeks of age and exhibit albuminuria at 3 months of age with mild increases in TNF- α expression and 3-NT accumulation in the aorta. Diabetes-induced significant increases in the wall thickness and structural derangement of aorta were found in OVE26 mice with significant increases in aortic oxidative and nitrosative damage, inflammation, and remodeling at 6 months of diabetes, but not at 3 months of diabetes. However, these pathological changes seen at the 6 months of diabetes were abolished in OVE26 mice treated with MG-132 for 3 months that were also associated with a significant increase in Nrf2 expression in the aorta as well as transcription of downstream genes. These results suggest that chronic treatment with low-dose MG132 can afford an effective therapy for diabetes-induced pathogenic changes in the aorta, which is associated with the increased Nrf2 expression and transcription.
authors.affiliation: The Second Hospital of Jilin University, Changchun 130041, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Miao
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Cui
authors.forename: Weixia
authors.initials: W
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Xin
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Lining
authors.initials: L
authors.lastname: Miao
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Fu
authors.forename: Guanfang
authors.initials: G
authors.lastname: Su
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D006943:Hyperglycemia / Q000209:etiology; D007976:Leupeptins / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007976:Leupeptins; D051267:NF-E2-Related Factor 2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde