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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 371 - 380 (10page)
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Doxorubicin is still main drug in chemotherapy with limitation of use due to adverse drug reaction. Increased oxidative stress and alteration of nitric oxide control have been involved in cardiotoxicity of doxorubicin (DOX). A Disintegrin And Metalloproteinase (ADAMs) are transmembrane ectoproteases to regulate cell-cell and cell-matrix interactions, but role in cardiac disease is unclear. The aim of this study was to determine whether DOX activates peroxynitrite and ADAM 10 and thus ADAM and matrix metalloproteinase (MMP) induce cardiac remodeling in DOX-induced cardiomyopathy. Adult male Sprague-Dawley rats were subjected to cardiomyopathy by DOX (6 times of 2.5 mg/kg DOX over 2-weeks), and were randomized as four groups. Then followed by 3, 5, 7, and 14 days after cessation of DOX injection. DOX-injected animals significantly decreased left ventricular fractional shortening compared with control by M-mode echocardiography. The expressions of cardiac nitrotyrosine by immunohistochemistry were significant increased, and persisted for 2 weeks following the last injection. The expression of eNOS was increased by 1.9 times (p<0.05), and iNOS was marked increased in DOX-heart compared with control (p<0.001). Compared to control rats, cardiac ADAM10- and MMP 9- protein expressions increased by 20 times, and active/total MMP 9 proteolytic activity showed increase tendency at day 14 after cessation of DOX injection (n=10, each group). DOX-treated $H_9C_2$ cell showed increased ADAM10 protein expression with dose-dependency (p<0.01) and morphometric changes showed the increase of ventricular interstitial, nonvascular collagen deposition. These data suggest that activation of cardiac peroxynitrite with increased iNOS expression and ADAM 10-dependent MMP 9 expression may be a molecular mechanism that contributes to left ventricular remodeling in DOXinduced cardiomyopathy.
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참고문헌 (31)
참고문헌 신청
Arndt, M. / 2002 / Altered expression of ADAMs(A Disintegrin And Metalloproteinase) in fi brillating human atria / Circulation 105:720~725
Ara, J. / 1998 / Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) / Proc. Natl. Acad Sci. U.S.A 95:7659~7663
Beckman, J. S / 1996 / Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly / Am J. Physiol 271:1424~1437
Black, R. A. / 1998 / ADAMS: focus on the protease domain / Current Opinion in Cell Biology 10:654~659
Cheung, P. Y. / 2000 / Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart / Circulation 101:1833~1839
Ara, J. / 1998 / Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) / Proc. Natl. Acad Sci. U.S.A 95:7659~7663
Beckman, J. S / 1996 / Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly / Am J. Physiol 271:1424~1437
Black, R. A. / 1998 / ADAMS: focus on the protease domain / Current Opinion in Cell Biology 10:654~659
Cheung, P. Y. / 2000 / Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart / Circulation 101:1833~1839
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