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Involvement of retinoic acid in adri...

Danelisen, Igor.

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Involvement of retinoic acid in adriamycin-induced cardiomyopathy.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Involvement of retinoic acid in adriamycin-induced cardiomyopathy./
作者:	Danelisen, Igor.
面頁冊數:	176 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0631.
Contained By:	Dissertation Abstracts International67-02B.
標題:	Biology, Animal Physiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR12256
ISBN:	9780494122563

Involvement of retinoic acid in adriamycin-induced cardiomyopathy.
Danelisen, Igor.

Involvement of retinoic acid in adriamycin-induced cardiomyopathy. - 176 p.

Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0631.

Thesis (Ph.D.)--University of Manitoba (Canada), 2006.

The occurrence of adriamycin-induced heart failure in observed animals was confirmed by clinical, hemodynamic and echocardiographic data.

ISBN: 9780494122563Subjects--Topical Terms:

1017835
Biology, Animal Physiology.

Involvement of retinoic acid in adriamycin-induced cardiomyopathy.
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100 1 $a Danelisen, Igor. $3 1281919
245 1 0 $a Involvement of retinoic acid in adriamycin-induced cardiomyopathy.
300 $a 176 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0631.
502 $a Thesis (Ph.D.)--University of Manitoba (Canada), 2006.
520 $a The occurrence of adriamycin-induced heart failure in observed animals was confirmed by clinical, hemodynamic and echocardiographic data.
520 $a Use of adriamycin, an anthracycline antineoplastic drug, is limited by the development of drug-induced cardiomyopathy and congestive heart failure. The most prominent factor involved in the pathogenesis of this drug-induced condition is oxidative stress and occurrence of apoptosis. However, the exact correlation between the adriamycin-induced oxidative stress, increased apoptosis and progression of drug-induced heart failure still remains to be established. Retinoic acid (RA) is an active form of vitamin A (retinol) which is involved in the regulation of number of essential genes. This is achieved by retinoic acid binding to two types of intranuclear retinoic acid super-receptors (RAR and RXR) and their corresponding isomers (alpha, beta and gamma). The role of retinoic acid in the regulation of apoptosis has been documented in a number of studies.
520 $a This study tests the hypothesis that oxidative stress induced apoptosis and heart failure due to adriamycin may be mediated by the changes in the RAR/RXR receptor ratio. We have conducted in vivo and in vitro experiments to characterize adriamycin-induced changes in oxidative stress, RAR and RXR receptors, PPAR delta receptors, expression of proapoptotic and antiapoptotic proteins, gene chip analysis and apoptosis. Influence of antioxidants probucol, trolox and RA on these adriamycin-induced changes was also studied.
520 $a Adriamycin-induced increase in the oxidative stress was found to cause an increase in the RAR/RXR receptor ratio which effected the expression of proapoptotic (Bax) and antiapoptotic proteins (Bcl-xl), thus resulting in an increase in the Bax/Bcl-xl ratio. The increase in Bax/Bcl-xl ratio led to an increase in apoptosis in cardiac myocytes. The treatment with antioxidants probucol (in vivo) and trolox (in vitro) caused a decrease in RAR/RXR ratio resulting in a decrease in the Bax/Bcl-xl ratio, thus preventing the occurrence of adriamycin-induced apoptosis.
520 $a It is concluded that adriamycin induced oxidative stress disrupts retinoic acid signaling processes resulting in an increase in RAR/RXR ratio. The changes in RAR/RXR receptor ratio correlated with the upregulation of pro-apoptosic proteins leading to apoptosis. This apoptosis may play a significant role in the pathogenesis of adriamycin-induced heart failure. (Abstract shortened by UMI.)
590 $a School code: 0303.
650 4 $a Biology, Animal Physiology. $3 1017835
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
690 $a 0433
710 2 0 $a University of Manitoba (Canada). $3 1018707
773 0 $t Dissertation Abstracts International $g 67-02B.
790 $a 0303
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR12256