G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats

Sarah M. White, Lauren M. North, Emily Haines, Megan Goldberg, Lydia M. Sullivan, Jeffrey D. Pressly, David S. Weber, Frank Park, Kevin R. Regner

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 vehicletreated 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. Copyright

Original languageEnglish (US)
Pages (from-to)369-377
Number of pages9
JournalMolecular pharmacology
Volume86
Issue number4
DOIs
StatePublished - Oct 1 2014

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Protein Subunits
Reperfusion Injury
GTP-Binding Proteins
Kidney
Reperfusion
Epithelial Cells
Heterotrimeric GTP-Binding Proteins
Proliferating Cell Nuclear Antigen
Bromodeoxyuridine
Fluorescein
S Phase
Acute Kidney Injury
Sprague Dawley Rats
gallein
Cell Cycle
Homeostasis
Ischemia
Epithelium
Maintenance
Control Groups

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

White, S. M., North, L. M., Haines, E., Goldberg, M., Sullivan, L. M., Pressly, J. D., ... Regner, K. R. (2014). G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats. Molecular pharmacology, 86(4), 369-377. https://doi.org/10.1124/mol.114.092346

G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats. / White, Sarah M.; North, Lauren M.; Haines, Emily; Goldberg, Megan; Sullivan, Lydia M.; Pressly, Jeffrey D.; Weber, David S.; Park, Frank; Regner, Kevin R.

In: Molecular pharmacology, Vol. 86, No. 4, 01.10.2014, p. 369-377.

Research output: Contribution to journalArticle

White, SM, North, LM, Haines, E, Goldberg, M, Sullivan, LM, Pressly, JD, Weber, DS, Park, F & Regner, KR 2014, 'G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats', Molecular pharmacology, vol. 86, no. 4, pp. 369-377. https://doi.org/10.1124/mol.114.092346
White SM, North LM, Haines E, Goldberg M, Sullivan LM, Pressly JD et al. G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats. Molecular pharmacology. 2014 Oct 1;86(4):369-377. https://doi.org/10.1124/mol.114.092346
White, Sarah M. ; North, Lauren M. ; Haines, Emily ; Goldberg, Megan ; Sullivan, Lydia M. ; Pressly, Jeffrey D. ; Weber, David S. ; Park, Frank ; Regner, Kevin R. / G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats. In: Molecular pharmacology. 2014 ; Vol. 86, No. 4. pp. 369-377.
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