Chronic inflammation alters production and release of glutathione and related thiols in Human U373 astroglial cells

Steele, Megan L., Fuller, Stacey, Maczurek, Annette E., Kersaitis, Cindy, Ooi, Lezanne, and Münch, Gerald (2013) Chronic inflammation alters production and release of glutathione and related thiols in Human U373 astroglial cells. Cellular and Molecular Neurobiology, 33 (1). pp. 19-30.

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Abstract

Neurons rely on glutathione (GSH) and its degradation product cysteinylglycine released by astrocytes to maintain their antioxidant defences. This is particularly important under conditions of inflammation and oxidative stress, as observed in many neurodegenerative diseases including Alzheimer's disease (AD). The effects of inflammatory activation on intracellular GSH content and the extracellular thiol profile (including cysteinylglycine and homocysteine) of astrocytes were investigated. U373 astroglial cells exposed to IL-1β and TNF-α for up to 96 h showed a dose-dependent increase in IL-6 release, indicative of increasing pro-inflammatory cellular activation. With increasing concentrations of IL-1β and TNF-α (0.01–1 ng/ml), an increase in both intracellular and extracellular GSH levels was observed, followed by a return to control levels in response to higher concentrations of IL-1β and TNF-α. Extracellular levels of cysteinylglycine decreased in response to all concentrations of IL-1β and TNF-α. In contrast, levels of the neurotoxic thiol homocysteine increased in a dose-dependent manner to IL-1β and TNF-α-induced activation. Our results suggest that chronically activated astrocytes in the brain might fail to adequately maintain GSH substrate delivery to neurons, thus promoting neuronal vulnerability. They might also explain the elevated levels of homocysteine found in the brains and serum of patients with AD.

Item ID: 25046
Item Type: Article (Research - C1)
ISSN: 1573-6830
Keywords: Astrocyte, Glutathione, Cysteinylglycine, Homocysteine, Inflammation, Alzheimer's disease
Funders: UWS, Alzheimer's Australia
Date Deposited: 20 Feb 2013 09:12
FoR Codes: 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030499 Medicinal and Biomolecular Chemistry not elsewhere classified @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 100%
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