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Induction of heme oxygenase 1 in radiation nephropathy: role of angiotensin II. Radiat Res 2001 May;155(5):734-9

Date

04/17/2001

Pubmed ID

11302771

DOI

10.1667/0033-7587(2001)155[0734:iohoir]2.0.co;2

Scopus ID

2-s2.0-0035002888 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Datta, P. K., Moulder, J. E., Fish, B. L., Cohen, E. P. and Lianos, E. A. Induction of Heme Oxygenase 1 in Radiation Nephropathy: Role of Angiotensin II. Radiat. Res. 155, 734-739 (2001). In a rat model of radiation-induced nephropathy, we investigated changes in expression of heme oxygenase 1 (Hmox1, also known as HO-1), an enzyme that catalyzes conversion of heme into biliverdin, carbon monoxide and iron. The study explored whether radiation induces Hmox1 expression in the irradiated kidney and whether angiotensin II (AII) mediates Hmox1 expression in glomeruli isolated from irradiated kidneys. To assess the effects of radiation on Hmox1 expression, rats received 20 Gy bilateral renal irradiation and were randomized to groups receiving an AII type 1 (AT(1)) receptor antagonist (L-158,809) or no treatment. Drug treatment began 9 days prior to bilateral renal irradiation and continued for the duration of the study. Estimation of Hmox1 levels in glomerular protein lysates assessed by Western blot analysis revealed a significant increase in Hmox1 protein at 50 and 65 days postirradiation. In animals treated with the AT(1) receptor antagonist, there was no induction of Hmox1, suggesting that AII may be a mediator of Hmox1 induction. To confirm that AII stimulates Hmox1 expression, animals were infused with 200, 400 or 800 ng/kg min(-1) of AII for 18-19 days, and Hmox1 protein levels in glomeruli were assessed. There was a significant induction of Hmox1 in glomeruli of animals infused with 800 ng/kg min(-1) of AII. These studies demonstrate that glomerular Hmox1 expression is elevated in the middle phase of radiation nephropathy and that AII can increase glomerular Hmox1 levels.

Author List

Datta PK, Moulder JE, Fish BL, Cohen EP, Lianos EA



MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Blood Pressure
Enzyme Induction
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Imidazoles
Kidney
Kidney Diseases
Rats
Tetrazoles
Transforming Growth Factor beta