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

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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.

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Abbreviations

DAN:

2,3-Diaminonaphthalene

DCF:

Dichlorofluorescein

DMEM:

Dulbecco’s modified Eagle medium

FBS:

Fetal bovine serum

GSH:

Glutathione

H2DCFDA:

2′,7′-Dichlorodihydrofluorescein diacetate

H2O2 :

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-diphenyl-tetrazolium bromide

NFκB:

Nuclear factor-kappaB

NO:

Nitric oxide

Nrf2:

NF-E2-related factor 2

PBS:

Phosphate-buffered saline

ROS:

Reactive oxygen species

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Acknowledgments

This work was supported by a grant from the KIEIKAI Research Foundation (to M. M.) and by JSPS KAKENHI Grant numbers 26450447 (to M. M.) and 15 K07768 (to Y. N.).

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Authors and Affiliations

  1. Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku Ourai Kita, Izumisano, Osaka, 598-8531, Japan

    Mitsuaki Moriyama, Ryosuke Kurebayashi, Kenji Kawabe, Katsura Takano & Yoichi Nakamura

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  1. Mitsuaki Moriyama
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  2. Ryosuke Kurebayashi
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  3. Kenji Kawabe
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  4. Katsura Takano
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Correspondence to Mitsuaki Moriyama.

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Moriyama, M., Kurebayashi, R., Kawabe, K. et al. Acetate Attenuates Lipopolysaccharide-Induced Nitric Oxide Production Through an Anti-Oxidative Mechanism in Cultured Primary Rat Astrocytes. Neurochem Res 41, 3138–3146 (2016). https://doi.org/10.1007/s11064-016-2038-2

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