Linked Life Data

20805291

Source:http://linkedlifedata.com/resource/pubmed/id/20805291

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-11-18
pubmed:abstractText
Nonalcoholic fatty liver disease (NAFLD), which occurs in approximately 17 to 40% of Americans, encompasses progressive stages of liver damage ranging from steatosis to nonalcoholic steatohepatitis (NASH). Inflammation and oxidative stress are known characteristics of NAFLD; however, the precise mechanisms occurring during disease progression remain unclear. The purpose of the current study was to determine whether the expression or function of enzymes involved in the antioxidant response, NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione transferase (GST), and glutamate cysteine ligase, are altered in the progression of human NAFLD. Human livers staged as normal, steatotic, NASH (fatty), and NASH (not fatty) were obtained from the Liver Tissue Cell Distribution System. NQO1 mRNA, protein, and activity tended to increase with disease progression. mRNA levels of the GST isoforms A1, A2, A4, M3, and P1 increased with NAFLD progression. Likewise, GST A and P protein increased with progression; however, GST M protein levels tended to decrease. Of interest, total GST activity toward the substrate 1-chloro-2,4-dinitrobenzene decreased with NAFLD progression. GSH synthesis does not seem to be significantly dysregulated in NAFLD progression; however, the GSH/oxidized glutathione redox ratio seemed to be reduced with disease severity, indicating the presence of oxidative stress and depletion of GSH throughout progression of NAFLD. Malondialdehyde concentrations were significantly increased with disease progression, further indicating the presence of oxidative stress. Nuclear immunohistochemical staining of nuclear factor E2-related factor 2 (Nrf2), an indicator of activation of the transcription factor, was evident in all stages of NAFLD. The current data suggest that Nrf2 activation occurs in response to disease progression followed by induction of specific Nrf2 targets, whereas functionality of specific antioxidant defense enzymes seems to be impaired as NAFLD progresses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2293-301
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural