Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-2-1
pubmed:abstractText
Both oxidative stress and epidermal growth factor (EGF) contribute to the initiation and progression of renal proximal tubular dysfunction under pathophysiologic conditions. Thus, this study was performed (1) to examine both the individual, and the combined effects of H2O2 and EGF on alpha-methyl-D-glucopyranoside uptake (alpha-MG uptake) in the primary cultured renal proximal tubule cells (PTCs), and (2) to elucidate the involvement of p44/42 mitogen activated protein kinase (MAPK) and phospholipase A2 in mediating these actions. Both H2O2 and EGF inhibited alpha-MG uptake individually, while the combination of H2O2 and EGF further potentiated the inhibitory effect on alpha-MG uptake, which was elicited by each agent. H2O2 not only caused a rapid increase in the phosphorylation of p44/42 MAPK, but also promoted the translocation of cytosolic phospholipase A2 (cPLA2) from the cytosolic to particulate fraction, and stimulated cellular [3H]-arachidonic acid (AA) release. EGF similarly activates phosphorylation of p44/42 MAPK and stimulates [3H]-AA release. When PTCs were exposed to 100 microM H2O2 and 50 ng/ml EGF simultaneously, a further increase in the phosphorylation of p44/42 MAPK, of [3H]-AA release, and of prostaglandin E2 (PGE2) production was elicited as compared with the effects of each individual agonist alone. Moreover, the additive phosphorylation of p44/42 MAPK, [3H]-AA release, and PGE2 production by H2O2 and EGF was almost completely inhibited by the p44/42 MAPK inhibitor, PD 98059. In conclusion, these results are consistent with the hypothesis that under conditions of oxidative stress, the H2O2-induced inhibition of alpha-MG uptake in the renal proximal tubule is mediated through a modulation of the EGF signaling pathway, promoting further phosphorylation of p44/42 MAPK, activation of PLA2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Methylglucosides, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Oxidants, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/Sodium, http://linkedlifedata.com/resource/pubmed/chemical/methylglucoside
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
203
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-25
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15368538-Animals, pubmed-meshheading:15368538-Arachidonic Acid, pubmed-meshheading:15368538-Cells, Cultured, pubmed-meshheading:15368538-Drug Interactions, pubmed-meshheading:15368538-Epidermal Growth Factor, pubmed-meshheading:15368538-Glucose, pubmed-meshheading:15368538-Hydrogen Peroxide, pubmed-meshheading:15368538-Kidney Tubules, Proximal, pubmed-meshheading:15368538-MAP Kinase Signaling System, pubmed-meshheading:15368538-Male, pubmed-meshheading:15368538-Methylglucosides, pubmed-meshheading:15368538-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:15368538-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:15368538-Oxidants, pubmed-meshheading:15368538-Oxidative Stress, pubmed-meshheading:15368538-Phospholipases A, pubmed-meshheading:15368538-Phospholipases A2, pubmed-meshheading:15368538-Rabbits, pubmed-meshheading:15368538-Sodium
pubmed:year
2005
pubmed:articleTitle
Effect of EGF on H2O2-induced inhibition of alpha-MG uptake in renal proximal tubule cells: involvement of MAPK and AA release.
pubmed:affiliation
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. hjhan@chonnam.ac.kr
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't