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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kelsen, Silvia Patel, Bijal J. Parker, Lawson B. Vera, Trinity Rimoldi, John M. Gadepalli, Rama S. V. Drummond, Heather A. Stec, David E. |
| Description | Country affiliation: United States Author Affiliation: Kelsen S ( Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.) |
| Abstract | Heme oxygenase (HO)-1 induction can attenuate the development of angiotensin II (ANG II)-dependent hypertension. However, the mechanism by which HO-1 lowers blood pressure is not clear. The goal of this study was to test the hypothesis that induction of HO-1 can reduce the ANG II-mediated increase in superoxide production in cultured thick ascending loop of Henle (TALH) cells. Studies were performed on an immortalized cell line of mouse TALH (mTALH) cells. HO-1 was induced in cultured mTALH cells by treatment with cobalt protoporphyrin (CoPP, 10 microM) or hemin (50 microM) or by transfection with a plasmid containing the human HO-1 isoform. Treatment of mTALH cells with 10(-9) M ANG II increased dihydroethidium (DHE) fluorescence (an index of superoxide levels) from 35.5+/-5 to 136+/-18 relative fluorescence units (RFU)/microm2. Induction of HO-1 via CoPP, hemin, or overexpression of the human HO-1 isoform significantly reduced ANG II-induced DHE fluorescence to 64+/-5, 64+/-8, and 41+/-4 RFU/microm2, respectively. To determine which metabolite of HO-1 is responsible for reducing ANG II-mediated increases in superoxide production in mTALH cells, cells were preincubated with bilirubin or carbon monoxide (CO)-releasing molecule (CORM)-A1 (each at 100 microM) before exposure to ANG II. DHE fluorescence averaged 80+/-7 RFU/microm2 after incubation with ANG II and was significantly decreased to 55+/-7 and 53+/-4 RFU/microm2 after pretreatment with bilirubin and CORM-A1. These results demonstrate that induction of HO-1 in mTALH cells reduces the levels of ANG II-mediated superoxide production through the production of both bilirubin and CO. |
| File Format | HTM / HTML |
| ISSN | 1931857X |
| e-ISSN | 15221466 |
| DOI | 10.1152/ajprenal.00057.2008 |
| Journal | AJP: Renal Physiology |
| Issue Number | 4 |
| Volume Number | 295 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2008-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Oxidative Stress Carbon Monoxide Cytology Bilirubin Discipline Physiology Heme Oxygenase-1 Genetics Physiology Loop Of Henle Protoporphyrins Cell Survival Rna, Small Interfering Cells, Cultured Discipline Nephrology Pharmacology Metabolism Drug Effects Animals Hemin Guanylate Cyclase Vasoconstrictor Agents Superoxides Mice Receptors, Cytoplasmic And Nuclear Angiotensin Ii Enzymology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Urology |
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