Formoterol restores mitochondrial and renal function after Ischemia-reperfusion injury

Sean R. Jesinkey, Jason A. Funk, L. Jay Stallons, Lauren P. Wills, Judit K. Megyesi, Craig C. Beeson, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renalmitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondrial biogenesis 24 hours after ischemia/reperfusion (I/R)-induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol, a potent, highly specific, and long-acting β2-adrenergic agonist, induces renalmitochondrial biogenesis in naivemice. Animalswere subjected to shamor I/Rinduced AKI, followed by once-daily intraperitoneal injection with vehicle or formoterol beginning 24 hours after surgery and continuing through 144 hours after surgery. Treatment with formoterol restored renal function, rescued renal tubules from injury, and diminished necrosis after I/R-induced AKI. Concomitantly, formoterol stimulatedmitochondrial biogenesis and restored the expression and function of mitochondrial proteins. Taken together, these results provide proof of principle that a novel drug therapy to treat AKI, and potentially other acute organ failures, works by restoring mitochondrial function and accelerating the recovery of renal function after injury has occurred.

Original languageEnglish (US)
Pages (from-to)1157-1162
Number of pages6
JournalJournal of the American Society of Nephrology
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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