Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease.

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Research Abstract Details 

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Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Abstract Text:

G D Zeevalk,L Manzino,P K Sonsalla,L P Bernard,

Parkinson's disease (PD) is associated with loss of total glutathione (GSH) which may contribute to progressive cell death. Peripheral GSH administration has been used clinically with reported benefits. Despite this, there is little specific information to characterize its cellular uptake or clearance, brain elevation with peripheral delivery or neuroprotective efficacy in PD models. The current study was carried out to provide this information using in vitro and in vivo approaches. In rat mesencephalic culture, the monoethyl ester of GSH (GEE), but not GSH (1-10 mM, 24 h) produced a dose-dependent elevation in GSH. The half-life for clearance was 10.14 h and was not different in cells depleted of GSH prior to loading. Elevation of GSH with GEE protected neurons from oxidative stress with H2O2 or metabolic stress with the complex I and II inhibitors MPP+ and malonate, respectively. To determine if peripheral administration of GEE could elevate brain GSH levels, rats were administered 0.1-50 mg/kg/day GEE via osmotic minipump either subcutaneously (sc) or via a cannula placed into the left cerebral ventricle (icv) for 28 days. Only central delivery of GEE resulted in significant elevations of brain GSH. Elevation of brain GSH by icv infusion of GEE was examined for its neuroprotective effects against chronic central delivery of MPP+. Infusion of 0.142 mg/kg/day MPP+ for 28 days caused a selective ipsilateral loss of striatal dopamine. Co-infusion of MPP+ with 10 mg/kg/day GEE significantly protected against striatal dopamine loss. These findings show that the ethyl ester of GSH but not GSH per se can elevate intracellular GSH, that brain elevation of GSH requires central delivery of the ethyl ester and that this elevation provides neuroprotection against oxidative stress or chronic mitochondrial impairment.

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Publishing Authors By Initials

GD Zeevalk,L Manzino,PK Sonsalla,LP Bernard,

For similar organic chemicals: carboxylic acids: acids, acyclic: butyric acids: aminobutyric acids: gamma-aminobutyric acid research abstracts see: organic chemicals: carboxylic acids: acids, acyclic: butyric acids: aminobutyric acids: gamma-aminobutyric acid research

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Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental neurology

VOLUME: 203

Page Numbers: 512-20

Journal Abbreviation: Exp. Neurol.

ISSN: 0014-4886

DAY: 17

MONTH: 10

YEAR: 2006

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370712

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Keywords Mesh Terms:

KEYWORDS: gamma-Aminobutyric Acid

MESH TERMS: metabolism

Chemical & Substance for Abstract: Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Information

Substance Name: Tyrosine 3-Monooxygenase

Registry Number: EC 1.14.16.2

Grant and Affiliation Information for Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease.

AFFILIATION: Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Building UBHC, Rm. 405D, 675 Hoes Lane, Piscataway, NJ 08854, USA. zeevalgd@umdnj.edu

Country: United States

AGENCY: United States NINDS

GRANT: R01 NS036157-07

ACRONYM: NS

MEDLINETA: Exp Neurol

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