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Advanced glycation end-products (AGE), RAGE and ROS accumulation in rat isolated arteries
Abstract   Peer reviewed

Advanced glycation end-products (AGE), RAGE and ROS accumulation in rat isolated arteries

Chenchel K Lonj, Shaun L Sandow and Timothy V Murphy
2013 Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Annual Scientific Meeting Book of Abstracts, p.89
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Annual Scientific Meeting Breaking down the silos - academia, industry and the government collaboratively developing medicines, 2013 (Melbourne, Australia, 01-Dec-2013–04-Dec-2013)
2013
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http://www.asceptasm.com/wp-content/uploads/2013/06/ASCEPT-abstracts-403-493.pdfView
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Abstract

Pharmacology and Pharmaceutical Sciences advanced glycation end-products (AGE) receptor for AGE (RAGE) reactive oxygen species (ROS)
Introduction. Hyperglycemia leads to excessive accumulation of AGE and deleterious effects on various tissues, including blood vessels. Some of these effects are mediated by the receptor for AGE (RAGE) and signalling involving accumulation of reactive oxygen species (ROS). Most studies on RAGE signalling have been performedin isolated cells; the present study examined AGE-induced ROS signalling in intact arteries. Aims. The aims of this study were to examine RAGE expression and the effect of glycated albumin on superoxide accumulation in arteries isolated from various vascular beds of the rat. Methods. The aorta, middle cerebral artery, second-order mesenteric artery and first-order cremaster muscle artery were dissected from 6wk-old male Sprague-Dawley rats (sodium thiopentone 100 mg/kg i.p.). RAGE expression was determined using immunohistochemistry (IHC). Superoxide was assayed using the luminescent reagent L-012. Artery segments were incubated with unglycated or glycated BSA (glycating agents methylglyoxal (MGO) or glucose-6-phosphate (G6P) for 40 min at 37°C prior to the L-012 assay. Results. RAGE expression was localised to the endothelium of the various artery types. RAGE expression was highest in the cremaster muscle artery, with lesser, similar levels of expression in the mesenteric and middle cerebral arteries, and a low level of expression in the aorta (n = 4 for each). Basal superoxide accumulation was highest in the middle cerebral artery, approximately double that observed in the cremaster muscle and mesenteric arteries with a very low amount of superoxide detected in the aorta (n = 6 for each). Superoxide accumulation was almost abolished by the NAD(P)H oxidase inhibitor apocynin (500 µM). Both MGO-BSA and G6P-BSA (0.1 mg/ml) inhibited superoxide accumulation in all vessels apart from the aorta; for example, MGO-BSA inhibited L-012 luminescence by 87±8 % in the middle cerebral artery (n = 6, P <0.05). MGO-BSA (0.1 mg/ml) inhibited superoxide accumulation only when applied to the intra-luminal surface of the vessels. Discussion. AGE inhibited superoxide accumulation in three of the vessels studied, presumably by inhibiting NAD(P)H oxidase. This effect did not appear to correlate with basal superoxide accumulation or RAGE expression.

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