{gamma}-Carboxyethyl hydroxychroman, a metabolite of {gamma}-tocopherol, preserves nitric oxide bioavailability in endothelial cells challenged with high glucose

We reported that supplementation with -tocopherol (-T) in humans limits impairments in endothelial function otherwise induced by postprandial hyperglycemia. Given the rapid metabolism of -T into -carboxyethyl hydroxychroman (-CEHC), we hypothesized that the vasoprotective activities of -T could be attributed to its metabolite -CEHC. To test this, human aortic endothelial cells (HAECs) treated with 0 (vehicle control) or 3 µM -CEHC for 24 h prior to incubation with normal (5 mM) or high (25 mM) glucose for 48 h. High-glucose increased levels of uncoupled endothelial nitric oxide synthase (eNOS) as evidenced by reduced (p < 0.05) eNOS dimer:monomer. High glucose also prevented insulin-stimulated increases in p-AktSer473: total Akt, p-eNOSSer1177: total eNOS, and NO• production. These adverse changes were accompanied by increased (p < 0.05) reactive oxygen species and mRNA expression of inflammatory mediators (VCAM-1, E-selectin, IL-8). However, each deleterious response evoked by high glucose was prevented when HAECs were incubated with -CEHC prior to the high glucose challenge. Taken together, our data support the hypothesis that vascular protection provided by -T in vivo may be elicited through the bioactivity of its metabolite, -CEHC. Furthermore, it is possible that the antioxidant and anti-inflammatory activities of -CEHC may mediate this protective activity.
Source: Experimental Biology and Medicine - Category: Research Authors: Tags: Endocrinology & amp;amp; Nutrition Source Type: research