Research Topics
Genomes and Genes | Paul S BrookesSummaryAffiliation: University of Rochester Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Mitochondria as a drug target in ischemic heart disease and cardiomyopathyAndrew M Walters
Department of Anesthesiology, Box 604, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642
Circ Res 111:1222-36. 2012..This review summarizes efforts to date in targeting mitochondria for ischemic heart disease and cardiomyopathy therapy and outlines emerging drug targets in this field...
Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transitionPaul S Brookes
Uiniversity of Alabama at Birmingham, Department of Pathology, 901 19th St South, Birmingham, AL 35294, USA
Am J Physiol Heart Circ Physiol 286:H39-46. 2004..These studies suggest protein targets revealed by Ca(2+) include dehydrogenases and CoA - containing enzymes. These data are discussed in the context of the role of mitochondria, Ca(2+), and ONOO(-) in apoptotic signaling...- Mitochondrial H(+) leak and ROS generation: an odd couplePaul S Brookes
Department of Anesthesiology, University of Rochester, Medical Center Box 604, 601 Elmwood Avenue, Rochester, NY 14642, USA
Free Radic Biol Med 38:12-23. 2005..Herein the molecular basis of both ROS generation and H(+) leak will be reviewed and the consequences of their interaction for mitochondrial function discussed... - A shortcut to mitochondrial signaling and pathology: a commentary on "Nonenzymatic formation of succinate in mitochondria under oxidative stress"Paul S Brookes
Department of Anesthesiology, University of Rochester Medical Center, Box 604, 601 Elmwood Avenue, Rochester, NY 14642, USA
Free Radic Biol Med 41:41-5. 2006 - Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditionsDavid L Hoffman
Department of Biochemistry, University of Rochester Medical Center, Rochester, NY 14642, USA
J Biol Chem 284:16236-45. 2009..Finally, the data set (see supplemental material) may be useful in the mathematical modeling of mitochondrial metabolism... - Reversible inhibition of cytochrome c oxidase by peroxynitrite proceeds through ascorbate-dependent generation of nitric oxideMaria Cecilia Barone
Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
J Biol Chem 278:27520-4. 2003..These observations are discussed in the context of ONOO-/ascorbate reactivity and the interaction of CcOX with reactive nitrogen species... - In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycineSergiy M Nadtochiy
Department of Anesthesiology, University of Rochester Medical Center, Rochester, NY 14620, USA
J Mol Cell Cardiol 46:960-8. 2009..Overall, these results are consistent with a role for mitochondrial S-nitrosation and complex I inhibition in the cardioprotective mechanism of IPC and SNO-MPG in vivo... - Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injurySergiy M Nadtochiy
Department of Anesthesiology, PO Box 604, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Mol Cell Cardiol 42:812-25. 2007..Overall these data suggest that mitochondrial S-nitrosation and complex I inhibition constitute a protective signaling pathway that is amenable to pharmacologic augmentation... - SIRT1-mediated acute cardioprotectionSergiy M Nadtochiy
Department of Anesthesiology, University of Rochester Medical Center, Rochester, New York 14642, USA
Am J Physiol Heart Circ Physiol 301:H1506-12. 2011.... - The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death mediated by the synthetic triterpenoid CDDO and its derivativesSteven H Bernstein
James P Wilmot Cancer Center, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
Blood 119:3321-9. 2012..Together, these findings suggest that Lon inhibition plays a contributory role in CDDO-induced lymphoma cell death, and support the concept that mitochondrial Lon is a novel anticancer drug target... - Mitochondria, nitric oxide, and cardiovascular dysfunctionAnup Ramachandran
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Free Radic Biol Med 33:1465-74. 2002..The interaction of NO with the various mitochondrial respiratory complexes and the role NO plays in modulating mitochondrial-mediated apoptosis in these systems will be discussed... - Cardioprotection by metabolic shut-down and gradual wake-upLindsay S Burwell
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
J Mol Cell Cardiol 46:804-10. 2009..This paper will review the evidence in support of this hypothesis, with a focus on inhibition of each of the mitochondrial respiratory complexes... - SLO-2 is cytoprotective and contributes to mitochondrial potassium transportAndrew P Wojtovich
Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America
PLoS ONE 6:e28287. 2011..These findings suggest that SLO2 contributes to protection from hypoxic injury by increasing the permeability of the mitochondrial inner membrane to K(+)... - Ischemic preconditioning: the role of mitochondria and agingAndrew P Wojtovich
Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Exp Gerontol 47:1-7. 2012..This review will summarize the effects of aging on myocardial IR injury and discuss relevant and emerging strategies to protect against MI with an emphasis on mitochondrial function... - Mechanisms of the interaction of nitroxyl with mitochondriaSruti Shiva
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Biochem J 379:359-66. 2004.... - Mitochondrial ATP-sensitive potassium channel activity and hypoxic preconditioning are independent of an inwardly rectifying potassium channel subunit in Caenorhabditis elegansAndrew P Wojtovich
Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
FEBS Lett 586:428-34. 2012..These data suggest that the mK(ATP) in C. elegans does not arise from a Kir derived channel... - NDUFS4: creation of a mouse model mimicking a Complex I disorderChristopher A Ingraham
Department of Biomedical Genetics, Univ of Rochester Medical Center, Rochester, NY, USA
Mitochondrion 9:204-10. 2009..Decreased Complex I activity with unaltered Complex II activity, along with an accumulation of lactate, were consistent with Complex I disorders in this mouse model... - The mitochondrial complex II and ATP-sensitive potassium channel interaction: quantitation of the channel in heart mitochondriaAndrew P Wojtovich
Department of Anesthesiology, University of Rochester Medical Center, NY, USA
Acta Biochim Pol 57:431-4. 2010..4 % of total complex II molecules are necessary to activate the mK(ATP). These results estimate the mK(ATP) content at 15 channels per mitochondrion... - Mitochondrial dysfunction in cardiac ischemia-reperfusion injury: ROS from complex I, without inhibitionAndrew J Tompkins
Departments of Anesthesiology, and Biochemistry and Molecular Biology, Box 604, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester NY 14642, USA
Biochim Biophys Acta 1762:223-31. 2006..These thiol modifications were accompanied by enhanced ROS generation from CxI, but not complex III. Implications for the pathology of cardiac I-R injury are discussed... - A novel mitochondrial K(ATP) channel assayAndrew P Wojtovich
Department of Pharmacology, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA
Circ Res 106:1190-6. 2010..The validity of current methods to assay mK(ATP) activity is disputed... - Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotectionSergiy M Nadtochiy
Department of Anesthesiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Biochem J 395:611-8. 2006..71). In conclusion, these data suggest that the modulation of H+ leak may have important implications for the outcome of IR injury... - Mitochondrial nitroalkene formation and mild uncoupling in ischaemic preconditioning: implications for cardioprotectionSergiy M Nadtochiy
Department of Anesthesiology, Box 604, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
Cardiovasc Res 82:333-40. 2009.... - A cell-based phenotypic assay to identify cardioprotective agentsStephanie Guo
School of Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA
Circ Res 110:948-57. 2012..The lack of clinical therapies for IR injury may be partly due to the difficulty of adapting IR injury models to high-throughput screening (HTS)... - Direct evidence for S-nitrosation of mitochondrial complex ILindsay S Burwell
Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14620, USA
Biochem J 394:627-34. 2006..The implications of these results for the physiological regulation of respiration, for reactive oxygen species generation and for a potential role of S-nitrosation in cardioprotection are discussed... - The endogenous mitochondrial complex II inhibitor malonate regulates mitochondrial ATP-sensitive potassium channels: implications for ischemic preconditioningAndrew P Wojtovich
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Biochim Biophys Acta 1777:882-9. 2008..Together, these observations suggest that complex II inhibition by endogenously formed malonate may represent an important activation pathway for mK(ATP) channels during IPC... - Purine release: a protective signaling mechanism of the mitochondrial permeability transition pore in ischemiaSergiy M Nadtochiy
Department of Anesthesiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Fiziol Zh 54:5-14. 2008..Both these events were inhibited by the PTP blockers cyclosporin A and sanglifehrin A. Implications for cardioprotective signaling by purines and the PTP are discussed... - An analysis of the effects of Mn2+ on oxidative phosphorylation in liver, brain, and heart mitochondria using state 3 oxidation rate assaysThomas E Gunter
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Toxicol Appl Pharmacol 249:65-75. 2010.... - The C. elegans mitochondrial K+(ATP) channel: a potential target for preconditioningAndrew P Wojtovich
Department of Pharmacology and Physiology, Box 604, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
Biochem Biophys Res Commun 376:625-8. 2008..Since C. elegans also exhibit IPC, our observations provide a framework to study the role of mK(ATP) in IR injury in a genetic model organism... - Modulation of cell surface protein free thiols: a potential novel mechanism of action of the sesquiterpene lactone parthenolideJolanta Skalska
James P Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States of America
PLoS ONE 4:e8115. 2009..Given recent data to suggest that the redox status of extracellular protein thiol groups (i.e. exofacial thiols) effects cell behavior, we hypothesized that redox active anti-cancer agents would modulate exofacial protein thiols... - Control of mitochondrial respiration by NO*, effects of low oxygen and respiratory statePaul S Brookes
Departments of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
J Biol Chem 278:31603-9. 2003..dependent spectral species in the respiratory chain in this state. These results are discussed in the context of regulation of respiration by NO. in vivo and its implications for the control of vessel-parenchymal O2 gradients... - The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial KATP channelsAndrew P Wojtovich
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA
Basic Res Cardiol 104:121-9. 2009..In conclusion, the specific complex II inhibitor AA5 is the most potent mK(ATP) activator discovered to date, and provides a novel method of activating mK(ATP) channels and protecting the heart from IR injury... - High throughput two-dimensional blue-native electrophoresis: a tool for functional proteomics of mitochondria and signaling complexesPaul S Brookes
Department of Pathology, University of Alabama at Birmingham, Biomedical Research Building 2, 901 19th Street South, Birmingham, AL 35294, USA
Proteomics 2:969-77. 2002..Applications of this functional mitochondrial proteomics method are discussed... - Calcium, ATP, and ROS: a mitochondrial love-hate trianglePaul S Brookes
University of Rochester Medical Center, 601 Elmwood Ave, Box 711, Rochester, NY 14642, USA
Am J Physiol Cell Physiol 287:C817-33. 2004..Overall, a "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction... - Mitochondrial Dok-4 recruits Src kinase and regulates NF-kappaB activation in endothelial cellsSeigo Itoh
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 280:26383-96. 2005..These data suggest a role for mitochondrial Dok-4 as an anchoring molecule for the tyrosine kinase c-Src, and in turn as a regulator of TNF-alpha-mediated ROS production and NF-kappaB activation... - Chronic alcohol consumption increases the sensitivity of rat liver mitochondrial respiration to inhibition by nitric oxideAparna Venkatraman
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Hepatology 38:141-7. 2003..We propose that this results in a greater vulnerability to hypoxia and the development of alcohol-induced hepatotoxicity... - Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: implications for hypoxic cell signalingDavid L Hoffman
Box 604 Anesthesiology, Univ of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA
Am J Physiol Heart Circ Physiol 292:H101-8. 2007..The implications for hypoxic cell signaling are discussed... - Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1Sergiy M Nadtochiy
Department of Anesthesiology, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 287:3573-80. 2012..Although the molecular mechanism linking ANT1-Cys(57) nitroalkylation and uncoupling is not yet known, these data suggest that ANT1-mediated uncoupling may be a mechanism for nitroalkene-induced cardioprotection... - Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injuryLindsay S Burwell
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
Antioxid Redox Signal 10:579-99. 2008..These direct effects of NO* on mitochondria are the focus of this review... - p90 ribosomal S6 kinase regulates activity of the renin-angiotensin system: a pathogenic mechanism for ischemia-reperfusion injuryXi Shi
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA
J Mol Cell Cardiol 51:272-5. 2011..Thus, renin inhibition may provide an alternative therapeutic strategy under conditions of increased RAS... - Measurement of mitochondrial respiratory thresholds and the control of respiration by nitric oxidePaul S Brookes
Department of Pathology, University of Alabama, Birmingham, Alabama 35294, USA
Methods Enzymol 359:305-19. 2002..Such experiments can provide insight into the intricate nature of the interaction between NO. and mitochondria and the variations in this system that can occur under both physiological and pathological conditions... - SIRT1 is a redox-sensitive deacetylase that is post-translationally modified by oxidants and carbonyl stressSamuel Caito
Department of Environmental Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 850, Rochester, NY 14642, USA
FASEB J 24:3145-59. 2010..Our data suggest that oxidants/aldehydes covalently modify SIRT1, decreasing enzymatic activity and marking the protein for proteasomal degradation, which has implications in inflammatory conditions... - Mitochondrial biotransformation of omega-(phenoxy)alkanoic acids, 3-(phenoxy)acrylic acids, and omega-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids: a prodrug strategy for targeting cytoprotective antioxidants to mitochondriaKurt S Roser
Mitochondrial Research and Innovation Group, Department of Anesthesiology, Rochester, NY 14642, USA
Bioorg Med Chem 18:1441-8. 2010..These results demonstrate that mitochondrial beta-oxidation is a potentially useful delivery system for targeting antioxidants to mitochondria... - The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and its derivatives elicit human lymphoid cell apoptosis through a novel pathway involving the unregulated mitochondrial permeability transition porePaul S Brookes
Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
Cancer Res 67:1793-802. 2007.... - Intra-myocyte ion homeostasis during ischemia-reperfusion injury: effects of pharmacologic preconditioning and controlled reperfusionJames E Davies
Department of Surgery, Birmingham, University of Alabama at Birmingham, 35294, USA
Ann Thorac Surg 76:1252-8; discussion 1258. 2003..05). CONCLUSIONS: Diazoxide and controlled reperfusion improved intra-myocyte Na(+) homeostasis after severe ischemia-reperfusion injury... - Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen speciesPaul S Brookes
Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Free Radic Biol Med 33:755-64. 2002.... - Lysine deacetylation in ischaemic preconditioning: the role of SIRT1Sergiy M Nadtochiy
Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 604, Rochester, NY 14642, USA
Cardiovasc Res 89:643-9. 2011..Lysine (Lys) acetylation is an important regulator of protein function, but this type of modification has not been studied in the context of IPC. We investigated Lys acetylation in IPC and its upstream regulation by SIRT1... - The coordinated increased expression of biliverdin reductase and heme oxygenase-2 promotes cardiomyocyte survival: a reductase-based peptide counters β-adrenergic receptor ligand-mediated cardiac dysfunctionBo Ding
University of Rochester School of Medicine and Dentistry, Department of Biochemistry and Biophysics, Rochester, NY 14642, USA
FASEB J 25:301-13. 2011..Finding that BVR and HO-2 levels, myocyte apoptosis, and contractile function of the heart can be modulated by small human BVR-based peptides offers a promising therapeutic approach for treatment of cardiac dysfunctions... - Modulation of mitochondrial adenosine triphosphate-sensitive potassium channels and sodium-hydrogen exchange provide additive protection from severe ischemia-reperfusion injuryStanley B Digerness
Department of Surgery, University of Alabama at Birmingham, Birmingham, Ala 35294-0007, USA
J Thorac Cardiovasc Surg 125:863-71. 2003..The putative mechanism for this benefit is superior protection of mitochondrial function... - Mitochondrial function in response to cardiac ischemia-reperfusion after oral treatment with quercetinPaul S Brookes
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 2180, USA
Free Radic Biol Med 32:1220-8. 2002..These results indicate that oral low dose quercetin is cardioprotective, possibly via a mechanism involving protection of mitochondrial function during I-R... - Oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate by complex IV of rat mitochondriaPaul S Brookes
Department of Pathology and Department of Nutrition Sciences, University of Alabama at Birmingham, 35294, USA
Biochemistry 41:5633-6. 2002.... 
Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transferSruti Shiva
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 204:2089-102. 2007..These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet...- Specific modification of mitochondrial protein thiols in response to oxidative stress: a proteomics approachTsu-Kung Lin
Department of Biochemistry, University of Otago, Box 56, Dunedin, New Zealand
J Biol Chem 277:17048-56. 2002..In addition the methodology has the potential to identify novel redox-dependent modulation of mitochondrial proteins... - Nanotransducers in cellular redox signaling: modification of thiols by reactive oxygen and nitrogen speciesChris E Cooper
Dept of Biological Sciences, University of Essex, Wivenhoe Park, CO4 3SQ, Colchester, UK
Trends Biochem Sci 27:489-92. 2002..The findings offer the enticing possibility that the cell can distinguish between different degrees of oxidant and nitrosative exposure by modification at a single site on a signaling molecule... - Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in ratsAna Guijarro
Dept of Surgery, University Hospital, 750 East Adams St, Syracuse, NY 13210, USA
Am J Physiol Regul Integr Comp Physiol 293:R1474-89. 2007..These events override the compensatory response to the drop in leptin levels aimed at conserving energy... - The basal proton conductance of mitochondria depends on adenine nucleotide translocase contentMartin D Brand
Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK
Biochem J 392:353-62. 2005..We conclude that half to two-thirds of the basal proton conductance of mitochondria is catalysed by the adenine nucleotide carrier, independently of its ATP/ADP exchange or fatty-acid-dependent proton-leak functions... - Sustained weight loss after Roux-en-Y gastric bypass is characterized by down regulation of endocannabinoids and mitochondrial functionAna Guijarro
Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York 13210, USA
Ann Surg 247:779-90. 2008..To determine the physiologic importance of endocannabinoids and mitochondrial function in the long-term outcome using a rat model of Roux-en-Y gastric bypass (RYGB) surgery... - Methods for measuring the regulation of respiration by nitric oxideSruti Shiva
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Methods Cell Biol 80:395-416. 2007
Research Grants
- Mitochondria & NO in Cardiac Ischemia-ReperfusionPaul Brookes; Fiscal Year: 2006..Realization of these aims will greatly enhance understanding of the basic mechanisms underlying mitochondrial perturbations in I-R leading to novel therapies. ..
- Mitochondria and NO? in Cardiac Ischemic PreconditioningPaul Brookes; Fiscal Year: 2009..It is anticipated that addressing Aims 1 & 2 will define new mechanisms by which NO mediates cardioprotection, and that Aim 3 will lead to novel therapies for the treatment of cardiac IR injury. ..
- Mitochondria and NO? in Cardiac Ischemic PreconditioningPaul S Brookes; Fiscal Year: 2010..It is anticipated that addressing Aims 1 &2 will define new mechanisms by which NO mediates cardioprotection, and that Aim 3 will lead to novel therapies for the treatment of cardiac IR injury. ..
- C. Elegans and Mitochondrial K+ ChannelsKEITH W NEHRKE; Fiscal Year: 2010..elegans. The identification of these molecules will help in the development of new therapies for heart attack and stroke. ..