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- Title
Effects of Chronic Angiotensin-H Infusion on Nuclear Factor-kappaB (NF-κB) Proteins in Aorta of Diabetic Mice.
- Authors
Feliciano-Matos, Juan; Tieu, Brian C.; Lejeune, Wanda S.; Yu, Yi-Hsuan E.; Ly, Brenda; Zhang, Xiaoquan; Tilton, Ronald G.
- Abstract
Angiotensin-II (Ang-II), the major effector peptide of the renin angiotensin system, potently accelerates progression of atherosclemsis and vascular remodeling, and induces activation of NF-κB, a nuclear transcription factor regulating expression of numerous proinflammatory and proangiogenic cytokines, chemokines, growth factors, and adhesion molecules. To investigate Ang-II effects on diabetes-induced vascular inflammation, effects of chronic Ang-II infusion on NF-κB canonical and noncanonical proteins were studied in aorta of type 2, three month hyperglycemic db/db mice and congenic age-matched controls. Proteins were extracted from buffer (containing protease and phosphatase inhibitors)-perfused aortas obtained from four experimental groups, including untreated and Ang-II-infused controls, and untreated and Ang-II-infused db/db mice. Ang-II was infused subcutaneously via osmotic mini-pumps (0.5 mg/kg/day) for one month after two months of untreated diabetes. Protein levels of canonical (RelA/p65, IκBα, IκBβ, IKKβ, p50) and noncanonical (NIK, RelB, IKKα, p52, TRAF3) NF-κB proteins were quantified by Western blotting and normalized to tissue beta actin levels using infrared imaging. After 3 months of diabetes, most NF-κB canonical proteins were decreased in abundance, including IKKβ (40 % decrease), p50 (32 %), IκBα (26 %); RelA/p65 (20 %), and IκBβ (16%). Similar decreases were observed for noncaoonical NF-κB proteins, including IKKα (46 %), RelB (36%), and TRAF3 (32%), while p52 was unchanged and NIK was increased ∼60 %. In general, Ang-II infusion into diabetic mice produced further decreases in canonical NF-κB proteins as well as p52 and TRAF3 (both decreased ∼65 %), but increased RelB 30%. Ang-II increased the total amount of kinases, including IKKα (31%), IKKβ (61%), and NIK (45%). These results indicate that steady state levels of most NF-κB proteins are decreased in aorta of diabetic mice, and suggest that Ang-II has a divergent effect on canonical versus non-canonical NF-κB proteins. ADA-Funded Research
- Subjects
INFUSION therapy; ANGIOTENSIN II; NF-kappa B; AORTA; PEOPLE with diabetes; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA609
- ISSN
0012-1797
- Publication type
Article