國家衛生研究院 NHRI:Item 3990099045/1409
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1409


    Title: Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide
    Authors: Zhu, YG;Carvey, PM;Ling, ZD
    Contributors: Division of Mental Health and Substance Abuse Research
    Abstract: We previously reported that injection of bacterial lipopolysaccharide (LPS) into gravid female rats at embryonic day 10.5 resulted in a birth of offspring with fewer than normal dopamine (DA) neurons along with innate immunity dysfunction and many characteristics seen in Parkinson's disease (PD) patients. The LPS-exposed animals were also more susceptible to secondary toxin exposure as indicated by an accelerated DA neuron loss, Glutathione (GSH) is an important antioxidant in the brain. A disturbance in glutathione homeostasis has been proposed for the pathogenesis of PD. In this study, animals prenatally exposed to LPS were studied along with an acute intranigral LPS injection model for the status of glutath one homeostasis, lipid peroxidation, and related enzyme activities. Both prenatal LPS exposure and acute LPS injection produced a significant GSH reduction and increase in oxidized GSH (GSSG) and lipid peroxide (LPO) production. Activity of gamma-glutamyleysteine synthetase (GCS), the rate-limiting enzyme in ale novo GSH synthesis, was up-regulated in acute supranigral LPS model but was reduced in the prenatal LPS model. The GCS light subunit protein expression was also down-regulated in prenatal LPS model. GSH redox recycling enzyme activities (glutathione peroxidase, GPx and glutathione reducdase, GR) and glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (gamma-GT) activities were all increased in prenatal LPS model. Prenatal LPS exposure and aging synergized in GSH level and GSH-related enzyme activities except for those (GR, GST, and gamma-GT) with significant regional variations. Additionally, prenatal LPS exposure produced a reduction of DA neuron count in the substantia nigra (SN). These results suggest that prenatal LPS exposure may cause glutathione homeostasis disturbance in offspring brain and render DA neurons susceptible to the secondary neurotoxin insult. (c) 2007 Elsevier Ltd. All rights reserved.
    Keywords: Biochemistry & Molecular Biology;Neurosciences
    Date: 2007-03
    Relation: Neurochemistry International. 2007 Mar;50(4):671-680.
    Link to: http://dx.doi.org/10.1016/j.neuint.2006.12.013
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0197-0186&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000245397000011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33847304640
    Appears in Collections:[Zaodung Ling(2006-2009)] Periodical Articles

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