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Titolo:
Oxidant stress activates AP-1 and heparin-binding epidermal growth factor-like growth factor transcription in renal epithelial cells
Autore:
Sakai, M; Tsukada, T; Harris, RC;
Indirizzi:
Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol,Med Ctr N S3223, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 r N S3223, Nashville, TN 37232 USA Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA Dept Vet Affairs Med Ctr Nashville TN USA 37212 , Nashville, TN 37212 USA
Titolo Testata:
EXPERIMENTAL NEPHROLOGY
fascicolo: 1, volume: 9, anno: 2001,
pagine: 28 - 39
SICI:
1018-7782(2001)9:1<28:OSAAAH>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; FACTOR MESSENGER-RNA; ACUTE TUBULAR-NECROSIS; NF-KAPPA-B; 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY; VASCULAR ENDOTHELIAL-CELLS; GENE-EXPRESSION; FACTOR-ALPHA; ATHEROSCLEROTIC PLAQUES; POSTISCHEMIC KIDNEY;
Keywords:
acute renal injury; oxidant stress; growth factor; gene transcription; epidermal growth factor; heparin-binding epidermal growth factor-like growth factor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, RC Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol,Med Ctr N S3223, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Nashville, TN 37232 USA
Citazione:
M. Sakai et al., "Oxidant stress activates AP-1 and heparin-binding epidermal growth factor-like growth factor transcription in renal epithelial cells", EXP NEPHROL, 9(1), 2001, pp. 28-39

Abstract

Ischemia/reperfusion injury increases the expression of bioactive heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the rat kidney, suggesting that oxidant stress or cell injury related to oxidant stressmight affect HB-EGF expression in the injured renal parenchyma. We utilized a nontransformed rat renal epithelial cell line (NRK-52E cells) to investigate whether reactive oxygen species induced transcriptional activation ofHB-EGF mRNA. Hypoxia/reoxygenation increased HB-EGF expression in NRK-52E cells, and at concentrations that induced sublethal cell injury, hydrogen peroxide (H2O2) increased HB-EGF mRNA expression 4.7-fold. The free radical scavengers, dimethylthiourea and N-acetylcysteine inhibited HB-EGF mRNA induction. In contrast, another free radical scavenger, pyrrolidine thiocarbamate (PDTC), augmented H2O2-mediated HB-EGF expression. Since PDTC has been reported to augment AP-l-mediated transcriptional activation, we utilized an electrophoretic mobility shift assay to confirm that H2O2 administration to NRK-52E cells did increase nuclear extract DNA-binding activity to a consensus AP-1 sequence. Using a CAT reporter assay coupled to the proximal 2,000 bp of the human HB-EGF 5'-untranslated region, we determined that H2O2 administration increased CAT activity 5.5-fold. Truncation or deletion mutations of a putative AP-1-binding site reduced the H2O2-stimulated activity by >60%, and there was increased DNA binding of nuclear extracts from H2O2-treated cells to a 24-bp oligonucleotide containing this putative AP-1 site. Anti-fos and jun antibodies inhibited this binding, and there was no binding to an oligonucleotide in which the putative AP-1 site was mutated. The site of the residual activation was found to exist in the most proximal 5'-untranslated region (-121 to +60), which contains two putative SP1 sites. Timing and localization of AP-l-binding activity from nuclear extracts from the post-ischemic tissue correlated with HB-EGF mRNA expression. Therefore,in renal epithelial cells, oxidant stress increases HB-EGF expression, which appears to be mediated in part by an increase in AP-1 binding. This activation may play an important role in the induction of HB-EGF mRNA in response to tissue injury and may regulate early stages of recovery following ischemic damage. Copyrighr (C) 2000 S. Karger AG, Basel.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:30:00