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'Wang,L.,W.Ma,R'Markovich,J'W'Chen'andP'H'Wang'1998a'"Regulationof cardiomyocyte apoptotic signaling by insulin-like growth factor I'" Circ'Res' 83:516-522. wang,L.,W.Ma,R.Markovich,w.L.Lee,andP.H.Wang.1998b'"Insulin-likegrowth factor I modulates induction of apoptotic signaling inH9C2 cardiac muscle cells'" Endo uinolo gY - 139 :13 5 4-I3 60' Wang,S., S.Kotamraju, E.Konorev, S.Kalivendi, J.Joseph, and B.Kalyanaraman. 2002b. ,,Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide'" Biochem'J. 367 :729-7 40 ' wang,X.D., G.W.Tang, J.G.Fox, N.I.Krinsky, and R.M.Russell' 1991. "Enz;'matic conversion of beta-carotene into beta-apo-carotenals and retinoids by human' monkey, ferret, and rat tissues.'' Arch'Biochem'Biophys' 285:8-16. Wayman,N.S', Y.Hattori, M.C.McDonald, H'Mota-Filipe, S.Cuzzocrea, B.Pisano, P.K.Chatterj ee, and c.Thiemerm am. 2002. "Li gands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size|' FASEB J' 16:1027-1040' V/ebster,K.A., D.J.Discher, S.Kaiser, O.Hernandez, B.Sato, and N'H.Bishopric' 1999' ,,Hypoxia-activated apoptosis of cardiac myocytes requires reoxygenation or a pH shift and is independent of p53." J.Clin.Invest.104:239-252. 'Weil,M., M.C.Raff, and V.M.Braga.1999. "Caspase activation in the terminal differentiation of human epidermal keratinocytes. " curr. BioI. 9 :3 6l -3 64' wikman-coffelt,J., M.Rapcsak, R.sievers, J.L.Rouleau, and w.w'Parmley' i983' "Verapamil, propranolol, and hydralazine protect against the acute cardiac depression induced by adriamy cin." cardiov as c. Res' 17 :43 -49' t72
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il\VOLVEMENT OF RETII\OIC ACID II{
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Title: AKNOWLEDGMENTS DEDICATION LI
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IV.b.3. The uptake to peripheral ti
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II.a. Total RAR and total RXR recep
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ACKNO\ryLEDGMENTS I must say that m
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DEDICATION To my toughest critic, m
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Figure: LIST OF FIGURES Page: 1. Ch
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30. A and B The expression of anti-
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treated (ADR), trolox treated (TROL
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INTRODUCTION Adriamycin, an anthrac
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apoptosis, which will ultimately pr
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LITERATURE REVIE\il I. Adriamycin i
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Binding and alkylation of DNA Inter
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myocardial inflammation which was s
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1990; Kusuoka et al. l99l; Olson et
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levels of antioxidant enzymes (Odom
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causing the increased leakage of el
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mechanisms which are involved in th
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to protect against adriamycin-induc
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The usage of Probucol.' Most promis
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II. Oxidative stress II.a. Introduc
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of a large array of cellular abnorm
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menstruation (Kokawa et al. 1996),
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DNA(Cohen 1997; Saikumar et al. 199
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pathogenesis of heart failure. A nu
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elonging to spontaneous hlpertensiv
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AlþTrsns Retlnolc Acld fAfRAl g€
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dehydrogenase (SDR), alcohol dehydr
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(Bavik et a|. 1991). Soon after its
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et al. 1994; Napoli 1996). The func
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is achieved through its binding to
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Retinoic acid signaling pathwaybegi
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(Bavik et al. 1997). One of the mos
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cells (Gaetano et ai. ZOot¡. The s
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neuroblastoma, genn cell tumors and
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presence of two distinctive pathway
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cytochrome C release from mitochond
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peroxidation (Sultana et a|.2004).
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adipose tissue and to a lesser exte
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such as; increased generation of re
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physiological and pathological proc
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Protective effects of PPAR y agonis
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IIYPOTHESIS This study tests the hy
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I.c.Collection of Tissues Hearts we
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thoracotomy was performed and heart
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Il.c.Western Blot Analvsis Western
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green were counted as dead cells. T
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RESULTS I.In Vivo Studies I.a.Gener
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Lc. Retinoic acid receptors Three w
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The RAR o and PPAR-õ receptors RNA
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significantly decreased when compar
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IL b.7. RAR alPha recePtor levels T
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ILb. 3. RAR sammø recEtor levels F
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ILb. 5. RXR baa recEúor levels The
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visible staining were accounted as
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DISSCUSION I. Adriamvcin CardiomvoP
Page 139 and 140: Treatment with adriamycin has been
Page 141 and 142: High RA 1 Adriamycin I oxidative st
Page 143 and 144: study as well as in others (Kumar e
Page 145 and 146: It is reported that PPAR y receptor
Page 147 and 148: expression. These effects of trolox
Page 149 and 150: REFERENCES Abdul Hamied,T.A., D.Par
Page 151 and 152: Bashor,M.M., D.O.Toft, and F.Chytll
Page 153 and 154: distribution of PPAR-alpha, -beta,
Page 155 and 156: colbert,M.C., D.G.Hall, T.R.Kimball
Page 157 and 158: Diep,Q.N., M'El Mabrouk, J.S.Cohn,
Page 159 and 160: Evans,R.M. 1988. "The steroid and t
Page 161 and 162: Ghione M. Development of Adriamycin
Page 163 and 164: Herman,E., R.Young, and S.Krop . Ig
Page 165 and 166: morphogenetic protein-2 inhibits se
Page 167 and 168: Khandoudi,N., P.Delerive, I.Berrebi
Page 169 and 170: Kusuoka,H., S.Futaki, Y.Koretsune,
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Page 173 and 174: Mehta,J.L., B.Hu, J.Chen, and D.Li.
Page 175 and 176: Morriss-Kay,G.M. and s.J.ward. 1999
Page 177 and 178: Notario,B., M.Zamora, O.Vinas, and
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Page 185 and 186: spiegelman,B.M. and J.s.Flier .1996
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Page 189: vanVeen,T.A.,H.V.vanRijen,R.F.V/ieg
Page 193 and 194: peroxisome proliferator-activated r
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