title: Subcellular Energetics and Metabolism: Potential Therapeutic Applications.
abstract: Part I of this review discussed the similarities between embryogenesis, mammalian adaptions to hypoxia (primarily driven by hypoxia-inducible factor-1 [HIF-1]), ischemia-reperfusion injury (and its relationship with reactive oxygen species), hibernation, diving animals, cancer, and sepsis, and it focused on the common characteristics that allow cells and organisms to survive in these states. Part II of this review describes techniques by which researchers gain insight into subcellular energetics and identify potential future tools for clinicians. In particular, P nuclear magnetic resonance to measure high-energy phosphates, serum lactate measurements, the use of near-infrared spectroscopy to measure the oxidation state of cytochrome aa3, and the ability of the protoporphyrin IX-triplet state lifetime technique to measure mitochondrial oxygen tension are discussed. In addition, this review discusses novel treatment strategies such as hyperbaric oxygen, preconditioning, exercise training, therapeutic gases, as well as inhibitors of HIF-1, HIF prolyl hydroxylase, and peroxisome proliferator-activated receptors.
authors.affiliation: From the Department of Anesthesiology, University of Virginia, Charlottesville, Virginia.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Thiele
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002248:Carbon Monoxide / Q000627:therapeutic use; D015687:Cell Hypoxia; D060833:Cellular Microenvironment; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005081:Exercise Therapy; D005740:Gases; D006801:Humans; D006862:Hydrogen Sulfide / Q000627:therapeutic use; D006931:Hyperbaric Oxygenation; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009569:Nitric Oxide / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism* / Q000627:therapeutic use*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D019265:Spectroscopy, Near-Infrared
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D005740:Gases; D051793:Hypoxia-Inducible Factor 1; D047492:Peroxisome Proliferator-Activated Receptors; D020011:Protective Agents; D009569:Nitric Oxide; D002248:Carbon Monoxide; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010100:Oxygen; D006862:Hydrogen Sulfide