Abstract |
Heterotrimeric G-proteins play a crucial role in the control of renal epithelial cell function during homeostasis and in response to injury. In this report, G-protein βγ subunit (Gβγ) dimer activity was evaluated during the process of tubular repair after renal ischemia-reperfusion injury (IRI) in male Sprague Dawley rats. Rats were treated with a small molecule inhibitor of Gβγ activity, gallein (30 or 100 mg/kg), 1 hour after reperfusion and every 24 hours for 3 additional days. After IRI, renal dysfunction was prolonged after the high-dose gallein treatment in comparison with vehicle treatment during the 7-day recovery period. Renal tubular repair in the outer medulla 7 days after IRI was significantly (P < 0.001) attenuated after treatment with high-dose gallein (100 mg/kg) in comparison with low-dose gallein (30 mg/kg), or the vehicle and fluorescein control groups. Gallein treatment significantly reduced (P < 0.05) the number of proliferating cell nuclear antigen-positive tubular epithelial cells at 24 hours after the ischemia-reperfusion phase in vivo. In vitro application of gallein on normal rat kidney (NRK-52E) proximal tubule cells significantly reduced (P < 0.05) S-phase cell cycle entry compared with vehicle-treated cells as determined by 5'-bromo-2'-deoxyuridine incorporation. Taken together, these data suggest that Gβγ signaling contributes to the maintenance and repair of renal tubular epithelium and may be a novel therapeutic target for the development of drugs to treat acute kidney injury.
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Authors | Sarah M White, Lauren M North, Emily Haines, Megan Goldberg, Lydia M Sullivan, Jeffrey D Pressly, David S Weber, Frank Park, Kevin R Regner |
Journal | Molecular pharmacology
(Mol Pharmacol)
Vol. 86
Issue 4
Pg. 369-77
(Oct 2014)
ISSN: 1521-0111 [Electronic] United States |
PMID | 25028481
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics. |
Chemical References |
- G-protein Beta gamma
- GTP-Binding Protein beta Subunits
- GTP-Binding Protein gamma Subunits
- Xanthenes
- gallein
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Topics |
- Animals
- Cardio-Renal Syndrome
(drug therapy, metabolism)
- Cell Line
- Cell Movement
- Cell Proliferation
- Epithelial Cells
(drug effects, metabolism, physiology)
- GTP-Binding Protein beta Subunits
(antagonists & inhibitors, metabolism)
- GTP-Binding Protein gamma Subunits
(antagonists & inhibitors, metabolism)
- Kidney
(drug effects, metabolism, pathology)
- Male
- Protein Multimerization
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(drug therapy, metabolism)
- Xanthenes
(pharmacology, therapeutic use)
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