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  • Title: Apocynin decreases AGEs-induced stimulation of NF-κB protein expression in vascular smooth muscle cells from GK rats.
    Author: Silva CO, da Silva OA, Duarte GP, Descomps B, Lahlou S.
    Journal: Pharm Biol; 2015 Apr; 53(4):488-93. PubMed ID: 25471209.
    Abstract:
    CONTEXT: Elevated oxidative stress plays a key role in diabetes-associated vascular disease. Excessive production of reactive oxygen species via advanced glycation end products (AGEs) activates peroxisome proliferator-activated receptor gamma (PPARγ) and the transcription factor nuclear factor-kB (NF-κB) in aortic vascular smooth muscle cells (VSMCs). Apocynin, a drug with an antioxidant effect, has also been proposed as a therapeutic agent for atherosclerotic disease. OBJECTIVES: This work investigates the effects of apocynin on the PPARγ and NF-κB protein expression evoked by AGEs in cultured VSMCs from Goto-Kakisaki (GK) rats, a non-obese insulin model of both insulin resistance and type 2 diabetes. MATERIALS AND METHODS: VSMCs, isolated from aortas of GK and non-diabetic rats, were cultured. The expression of proteins was evaluated by Western blot. The blood glucose concentration was measured with a blood glucose test meter. The diabetes of GK rats was controlled by blood glucose and insulin determinations (non-fasting values). The serum insulin concentration was determined by radioimmunoassay. RESULTS: In VSMCs from non-diabetic and GK rats, apocynin (1 and 10 µM) abolished the protein overexpression of NF-κB induced by glycated bovine serum albumin (AGEs-BSA) incubation. However, apocynin (1 and 10 µM) enhanced the expression of PPARγ protein in the presence of AGEs-BSA (100 μg/mL) in VSMCs from non-diabetic, but not from GK rats. CONCLUSION: These findings suggest that apocynin decreases the incidence of alterations in VSMCs induced by AGEs through the reduction of NF-κB and may represent an attractive therapeutic approach to treat diabetes mellitus.
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