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Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway
Descriptive
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Title
Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway
Name
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NamePart
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Hadzimichalis
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Norell Melissa
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Norell Melissa Hadzimichalis
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(authority = RUETD)
author
Name
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Merrill
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Gary
Affiliation
Advisory Committee
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Gary F Merrill
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(authority = RULIB)
chair
Name
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NamePart
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Firestein
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Bonnie
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Advisory Committee
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Bonnie L Firestein
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(authority = RULIB)
co-chair
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NamePart
(type = family)
Ma
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Jianjie
Affiliation
Advisory Committee
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Jianjie Ma
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(authority = RULIB)
internal member
Name
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Bagnell
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Carol
Affiliation
Advisory Committee
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Carol A Bagnell
Role
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(authority = RULIB)
internal member
Name
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NamePart
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McHugh
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Nansie
Affiliation
Advisory Committee
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Nansie A McHugh
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(authority = RULIB)
outside member
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Rutgers University
Role
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degree grantor
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NamePart
Graduate School - New Brunswick
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school
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Text
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theses
OriginInfo
DateCreated
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2008
DateOther
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2008-05
Language
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English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
ix, 82 pages
Abstract
Historically, acetaminophen has been employed as a safe and effective analgesic and antipyretic agent. However, our laboratory has recently reported that acetaminophen also confers functional cardioprotection following cardiac insult, including ischemia/reperfusion, hypoxia/reoxygenation, and exogenous peroxynitrite and hydrogen peroxide administration. In the current study, we examined the mechanism of acetaminophen-mediated cardioprotection following ischemia/reperfusion injury. Langendorff-perfused guinea pig hearts were exposed to acute treatment with acetaminophen (0.35 mM) or vehicle (Krebs-Henseleit buffer) beginning at 15 minutes of a 30-minute baseline stabilization period. Low-flow global myocardial ischemia was subsequently induced for 30 minutes followed by 60 minutes of reperfusion. Upon completion of reperfusion, hearts were homogenized and separated into cytosolic and mitochondrial fractions. Mitochondrial swelling and mitochondrial cytochrome c release were assessed and found to be significantly and completely reduced following reperfusion in acetaminophen-treated hearts when compared to vehicle. In a separate group of hearts, ventricular myocytes were isolated and subjected to fluorescence-activated cell sorting. Acetaminophen-treated hearts showed a significant decrease in late stage apoptotic myocytes when compared to vehicle-treated hearts following injury (58 [plus/minus] 1% vs. 81 [plus/minus] 5%, respectively). These data, together with electron micrograph analysis, suggest that acetaminophen mediates cardioprotection, in part, by inhibiting the mitochondrial permeability transition pore and subsequent apoptotic pathway.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 73-79).
Subject
(ID = SUBJ1);
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Topic
Physiology and Integrative Biology
Subject
(ID = SUBJ2);
(authority = ETD-LCSH)
Topic
Acetaminophen
Subject
(ID = SUBJ3);
(authority = ETD-LCSH)
Topic
Mitochondria
Subject
(ID = SUBJ4);
(authority = ETD-LCSH)
Topic
Heart--Effect of drugs on
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17322
Identifier
ETD_749
Location
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NjNbRU
Identifier
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doi:10.7282/T3RN386M
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
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Name
Norell Hadzimichalis
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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Type
Permission or license
Detail
Non-exclusive ETD license
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License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Technical
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1616384
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application/x-tar
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