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035 a| (Sirsi) o951120125;

035 a| (OCoLC)951120125;

049 a| EREE;

100 1 a| Alleman, Rick J.,e| author.?| UNAUTHORIZED;

245 10 a| Cardioprotective mechanisms targeting thiol redox homeostasis and mitochondrial bioenergetics /c| by Rick J. Alleman.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2016.;

300 a| 135 pages :b| illustrations.;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 15.35 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph.D.c| East Carolina Universityd| 2016.;

500 a| Presented to the faculty of the Department of Physiology.;

500 a| Advisor: David A. Brown.;

500 a| Title from PDF t.p. (viewed July 13, 2016).;

520 3 a| Coronary heart disease is a leading cause of death in the United States, totaled mostly by deaths associated with myocardial infarction and fatal ventricular arrhythmias. The inability to predict the occurrence of these pathologies due to their sudden and transient etiologies has hindered successful translation of therapies to the clinic. Given the multi-billion-dollar economic burden that cardiovascular disease exerts, it would be beneficial to further our knowledge on ways to better treat acute coronary syndromes. The goal of this work is to determine how mitochondria impact cardiac ischemia/reperfusion (I/R) injury, and to identify potential mechanisms to therapeutically target. The studies within were conducted on treadmill-trained male rats, ex vivo heart preparations, isolated/cell cultures, and isolated mitochondria. Herein demonstrates a strong link between susceptibility to I/R injury and cardioprotection through the manipulation of mitochondrial thiol status. Hearts from exercised rats were better protected from ischemic insults, and this coincided with preserved thiol redox homeostasis and greater stability in mitochondrial bioenergetics. The maintenance of mitochondria thiol was demonstrated through preservation of glutathione, which is a key redox control point in cardiac bioenergetics. When the thiol pool becomes more oxidized following oxidative stress, loss of mitochondrial membrane potential and collapsed bioenergetics increase susceptibility to I/R injury. Glutathione reductase helps maintain cell redox homeostasis by maintaining glutathione in a reduced form, where it can be utilized in ROS scavenging and redox signaling. In cell models of hypoxia/reoxygenation, targeting glutathione reductase expression influences the cells sensitivity to mitochondrial dysfunction. Several hallmark features of the cardioprotective phenotype include reductions in myocardial infarction, resistance to arrhythmic stimuli, lower ROS accumulation, and preserved mitochondrial function. Taken together, data from the studies suggest that targeting mitochondrial function during I/R, and more specifically, targeting mitochondrial thiol homeostasis, may have beneficial affects on treating coronary heart disease symptoms.;

504 a| Includes bibliographical references.;

650 2 a| Mitochondria.=| ^A917755;

650 2 a| Energy Metabolism.=| ^A918215;

650 2 a| Homeostasis.=| ^A919935;

650 2 a| Oxidation-Reduction.=| ^A919450;

650 2 a| Sulfhydryl Compounds.=| ^A1001585;

653 a| Bioenergetics;

653 a| Cardiac;

653 a| Exercise;

653 a| Ischemia/reperfusion;

653 a| Reactive oxygen species;

700 1 a| Brown, David A.,e| degree supervisor.=| ^A720682;

710 2 a| East Carolina University.b| Department of Physiology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/5401;

949 o| wjh;

994 a| C0b| ERE;

096 a| WG 300;

596 a| 1 4;

998 a| 4407981;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4407981-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 6/3/2016x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4407981-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 6/3/2016x| ETDz| HERESOURCE;

Cardioprotective mechanisms targeting thiol redox homeostasis and mitochondrial bioenergetics / by Rick J. Alleman.

Author/creator	Alleman, Rick J. author.
Other author	Brown, David A., degree supervisor.
Other author	East Carolina University. Department of Physiology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2016.
Description	135 pages : illustrations.
Supplemental Content	Access via ScholarShip
Subjects	Mitochondria. Energy Metabolism. Homeostasis. Oxidation-Reduction. Sulfhydryl Compounds.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Coronary heart disease is a leading cause of death in the United States, totaled mostly by deaths associated with myocardial infarction and fatal ventricular arrhythmias. The inability to predict the occurrence of these pathologies due to their sudden and transient etiologies has hindered successful translation of therapies to the clinic. Given the multi-billion-dollar economic burden that cardiovascular disease exerts, it would be beneficial to further our knowledge on ways to better treat acute coronary syndromes. The goal of this work is to determine how mitochondria impact cardiac ischemia/reperfusion (I/R) injury, and to identify potential mechanisms to therapeutically target. The studies within were conducted on treadmill-trained male rats, ex vivo heart preparations, isolated/cell cultures, and isolated mitochondria. Herein demonstrates a strong link between susceptibility to I/R injury and cardioprotection through the manipulation of mitochondrial thiol status. Hearts from exercised rats were better protected from ischemic insults, and this coincided with preserved thiol redox homeostasis and greater stability in mitochondrial bioenergetics. The maintenance of mitochondria thiol was demonstrated through preservation of glutathione, which is a key redox control point in cardiac bioenergetics. When the thiol pool becomes more oxidized following oxidative stress, loss of mitochondrial membrane potential and collapsed bioenergetics increase susceptibility to I/R injury. Glutathione reductase helps maintain cell redox homeostasis by maintaining glutathione in a reduced form, where it can be utilized in ROS scavenging and redox signaling. In cell models of hypoxia/reoxygenation, targeting glutathione reductase expression influences the cells sensitivity to mitochondrial dysfunction. Several hallmark features of the cardioprotective phenotype include reductions in myocardial infarction, resistance to arrhythmic stimuli, lower ROS accumulation, and preserved mitochondrial function. Taken together, data from the studies suggest that targeting mitochondrial function during I/R, and more specifically, targeting mitochondrial thiol homeostasis, may have beneficial affects on treating coronary heart disease symptoms.
General note	Presented to the faculty of the Department of Physiology.
General note	Advisor: David A. Brown.
General note	Title from PDF t.p. (viewed July 13, 2016).
Dissertation note	Ph.D. East Carolina University 2016.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Cardioprotective mechanisms targeting thiol redox homeostasis and mitochondrial bioenergetics / by Rick J. Alleman.

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