title: Molecular mechanisms of ischemic preconditioning in the kidney.
abstract: More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review.
authors: Departments of Medicine, Anatomy and Cell Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; pkapitsinou@kumc.edu.
authors: Pinelopi P
authors: PP
authors: Kapitsinou
authors: Departments of Medicine, Cancer Biology, and Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and Medicine and Research Services, Department of Veterans Affairs Hospital, Tennessee Valley Healthcare System, Nashville, Tennessee.
authors: Volker H
authors: http://orcid.org/0000-0002-7051-8994
authors: VH
authors: Haase
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007668:Kidney / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D051793:Hypoxia-Inducible Factor 1
keywords: HIF prolyl-4-hydroxylases; acute kidney injury; adenosine; dioxygenases; erythropoietin; hypoxia; hypoxia-inducible factor; inflammation; ischemic preconditioning; oxygen sensing