Acetate Attenuates Lipopolysaccharide-Induced Nitric Oxide Production Through an Anti-Oxidative Mechanism in Cultured Primary Rat Astrocytes (original) (raw)

2016, Neurochemical Research

Abbreviations DAN 2,3-Diaminonaphthalene DCF Dichlorofluorescein DMEM Dulbecco's modified Eagle medium FBS Fetal bovine serum GSH Glutathione H 2 DCFDA 2′,7′-Dichlorodihydrofluorescein diacetate H 2 O 2 Hydrogen peroxide HBS Hepes-buffered saline iNOS Inducible nitric oxide synthase LPS Lipopolysaccharide MAPK Mitogen-activated protein kinase MTT 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide NFκB Nuclear factor-kappaB NO Nitric oxide Nrf2 NF-E2-related factor 2 PBS Phosphate-buffered saline ROS Reactive oxygen species Introduction Acetate, the main constituent of vinegar, represents a class of biomolecules that is usually found in low concentrations (<1 mmol/L) in blood plasma and is readily transported into cells. Acetyl-CoA, a metabolite of acetate, is a substrate of many molecules including glucose, ketone bodies, cholesterol, acetylcholine, and fatty acids, and is also oxidized in the citric acid cycle during the production of ATP. Recent investigations have unveiled new roles for acetate in cell metabolism. Acetate is readily consumed to meet the demands for growth and proliferation in several types of cancer cells [1] and in embryonic stem cells [2]. Acetate increases the supply of acetyl-CoA due to the action Abstract The biomolecule acetate can be utilized for energy production, lipid synthesis, and several metabolic processes. Acetate supplementation reduces neuroglial activation in a model of neuroinflammation induced by intraventricular injection of lipopolysaccharide (LPS). To investigate the mechanisms underlying the anti-inflammatory effect of acetate on glial cells, we examined the effect of acetate on nitric oxide (NO) production, which was experimentally activated by LPS, in cultured primary rat astrocytes. Acetate attenuated the LPS-induced NO production in a dose-dependent manner, although cell viability was not affected. Acetate suppressed the phosphorylation of p38-mitogen-activated protein kinase 24 h after LPS treatment. Acetate decreased the LPS-induced production of intracellular reactive oxygen species (ROS) at 4-24 h concomitant with an increase in glutathione. Acetate rescued astrocytes from the hydrogen peroxide-induced cell death by reducing ROS levels. These findings suggest that attenuation of NO production by acetate may alleviate glial cell damage during neuroinflammation. Acetate may offer a glioprotective effect through an anti-oxidative mechanism.