Linked Life Data

19156441

Source:http://linkedlifedata.com/resource/pubmed/id/19156441

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-20
pubmed:abstractText
Elevated glutamate levels have been reported in humans with diabetic retinopathy. Retinal Müller glial cells regulate glutamate levels via the GLAST transporter and system x(c)(-) (cystine-glutamate exchanger). We have investigated whether transporter function and gene and/or protein expression are altered in mouse Müller cells cultured under conditions of hyperglycemia or oxidative stress (two factors implicated in diabetic retinopathy). Cells were subjected to hyperglycemic conditions (35 mM glucose) over an 8-day period or to oxidative stress conditions (induced by exposure to various concentrations of xanthine:xanthine oxidase) for 6 h. The Na(+)-dependent and -independent uptake of [(3)H] glutamate was assessed as a measure of GLAST and system x(c)(-) function, respectively. Hyperglycemia did not alter the uptake of [(3)H] glutamate by GLAST or system x(c)(-); neither gene nor protein expression decreased. Oxidative stress (70:14 or 100:20 microM xanthine:mU/ml xanthine oxidase) decreased GLAST activity by approximately 10% but increased system x(c)(-) activity by 43% and 89%, respectively. Kinetic analysis showed an oxidative-stress-induced change in V(max), but not K(m). Oxidative stress caused a 2.4-fold increase in mRNA encoding xCT, the unique component of system x(c)(-). Of the two isoforms of xCT (40 and 50 kDa), oxidative stress induced a 3.6-fold increase in the 40-kDa form localized to the plasma membrane. This is the first report of the differential expression and localization of xCT isoforms as caused by cellular stress. Increased system x(c)(-) activity in Müller cells subjected to conditions associated with diabetic retinopathy may be beneficial, as this exchanger is important for the synthesis of the antioxidant glutathione.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1432-0878
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
335
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
477-88
pubmed:dateRevised
2011-5-12
pubmed:meshHeading
pubmed-meshheading:19156441-Amino Acid Transport System y+, pubmed-meshheading:19156441-Animals, pubmed-meshheading:19156441-Blood Glucose, pubmed-meshheading:19156441-Cells, Cultured, pubmed-meshheading:19156441-Excitatory Amino Acid Transporter 1, pubmed-meshheading:19156441-Female, pubmed-meshheading:19156441-Gene Expression, pubmed-meshheading:19156441-Glutamic Acid, pubmed-meshheading:19156441-Humans, pubmed-meshheading:19156441-Hyperglycemia, pubmed-meshheading:19156441-Immunohistochemistry, pubmed-meshheading:19156441-Male, pubmed-meshheading:19156441-Mice, pubmed-meshheading:19156441-Mice, Inbred C57BL, pubmed-meshheading:19156441-Neuroglia, pubmed-meshheading:19156441-Oxidative Stress, pubmed-meshheading:19156441-Retina, pubmed-meshheading:19156441-Vimentin, pubmed-meshheading:19156441-Xanthine, pubmed-meshheading:19156441-Xanthine Oxidase
pubmed:year
2009
pubmed:articleTitle
Effects of hyperglycemia and oxidative stress on the glutamate transporters GLAST and system xc- in mouse retinal Müller glial cells.
pubmed:affiliation
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural