title: Formoterol restores mitochondrial and renal function after ischemia-reperfusion injury.
abstract: Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial 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 renal mitochondrial biogenesis in naive mice. Animals were subjected to sham or I/R-induced 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 stimulated mitochondrial 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.
authors: Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina;
authors: Sean R
authors: SR
authors: Jesinkey
authors: Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina;
authors: Jason A
authors: JA
authors: Funk
authors: Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina;
authors: L Jay
authors: LJ
authors: Stallons
authors: Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina;
authors: Lauren P
authors: LP
authors: Wills
authors: Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
authors: Judit K
authors: JK
authors: Megyesi
authors: Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina;
authors: Craig C
authors: CC
authors: Beeson
authors: Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina.
authors: Rick G
authors: RG
authors: Schnellmann
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004983:Ethanolamines; D000068759:Formoterol Fumarate
keywords: acute renal failure; ischemia-reperfusion; mitochondria; proximal tubule; renal function; renal tubular epithelial cells