 | HEART IN STRESS
Copyright © 1999 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 874:156-168 (1999)
© 1999 New York Academy of Sciences
Apoptosis in Isolated Adult Cardiomyocytes Exposed to Adriamycina
DINENDER KUMAR,
LORRIE KIRSHENBAUM,
TIMAO LI,
IGOR DANELISEN AND
PAWAN SINGALb
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, R2H 2A6, Canada
aThis study was supported by a grant from the Manitoba Heart and Stroke Foundation. Dr. Kirshenbaum was supported by a scholarship from the Heart and Stroke Foundation of Canada and Dr. Singal by a salary award from the Medical Research Council of Canada.
bAddress correspondence to: Dr. Pawan K. Singal, Ph.D., D.Sc., F.A.C.C., Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Room R3022, Winnipeg, Manitoba R2H 2A6 Canada; Telephone: (204) 235-3416; Fax: (204) 233-6723; E-mail: psingal{at}sbrc.umanitoba.ca
Adriamycin (doxorubicin) is a highly potent antineoplastic agent, but its use is limited by the risk of developing cardiomyopathy and congestive heart failure. Available evidence suggests that adriamycin-induced congestive heart failure is mediated by oxidative stress. We examined the possibility of adriamycin-induced apoptosis in isolated adult rat cardiomyocytes and its inhibition by trolox, a water-soluble antioxidant. Cardiomyocytes isolated from rat hearts were exposed to 20 µM adriamycin for 1 h and examined at different post-treatment durations (0-23 h). Adriamycin caused a significant decrease in rod-shaped cells and an increase in round cells. Both Hoechst 33258 staining and TUNEL assay revealed a significantly increased number of apoptotic myocytes and nucleosomal fragmentation upon exposure to adriamycin. In agarose gel electrophoresis, DNA laddering was found to be more intense in adriamycin-exposed myocytes. A bright smear at the leading edge of the gels suggested indiscriminate fragmentation of DNA and myocyte necrosis by adriamycin. Both types of DNA degradations due to adriamycin were significantly reduced by trolox. We suggest that adriamycin-induced cell death involves both apoptosis and necrosis and these may be mediated by oxidative stress.
This article has been cited by other articles:
|
|
|
|
 
D. K. Singla, R. D. Singla, and D. E. McDonald
Factors released from embryonic stem cells inhibit apoptosis in H9c2 cells through PI3K/Akt but not ERK pathway
Am J Physiol Heart Circ Physiol,
August 1, 2008;
295(2):
H907 - H913.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Montero, A. Morales, L. Llacuna, J. M. Lluis, O. Terrones, G. Basanez, B. Antonsson, J. Prieto, C. Garcia-Ruiz, A. Colell, et al.
Mitochondrial Cholesterol Contributes to Chemotherapy Resistance in Hepatocellular Carcinoma
Cancer Res.,
July 1, 2008;
68(13):
5246 - 5256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Banyasz, I. Lozinskiy, C. E. Payne, S. Edelmann, B. Norton, B. Chen, Y. Chen-Izu, L. T. Izu, and C. W. Balke
Transformation of adult rat cardiac myocytes in primary culture
Exp Physiol,
March 1, 2008;
93(3):
370 - 382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Clerk, T. J. Kemp, G. Zoumpoulidou, and P. H. Sugden
Cardiac myocyte gene expression profiling during H2O2-induced apoptosis
Physiol Genomics,
April 24, 2007;
29(2):
118 - 127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Chicco, C. M. Schneider, and R. Hayward
Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart
Am J Physiol Regulatory Integrative Comp Physiol,
August 1, 2005;
289(2):
R424 - R431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Lou, I. Danelisen, and P. K. Singal
Involvement of mitogen-activated protein kinases in adriamycin-induced cardiomyopathy
Am J Physiol Heart Circ Physiol,
April 1, 2005;
288(4):
H1925 - H1930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Childs, S. L. Phaneuf, A. J. Dirks, T. Phillips, and C. Leeuwenburgh
Doxorubicin Treatment in Vivo Causes Cytochrome c Release and Cardiomyocyte Apoptosis, As Well As Increased Mitochondrial Efficiency, Superoxide Dismutase Activity, and Bcl-2:Bax Ratio
Cancer Res.,
August 15, 2002;
62(16):
4592 - 4598.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Liu, Z. Chen, C. C. Chua, Y.-S. Ma, G. A. Youngberg, R. Hamdy, and B. H. L. Chua
Melatonin as an effective protector against doxorubicin-induced cardiotoxicity
Am J Physiol Heart Circ Physiol,
July 1, 2002;
283(1):
H254 - H263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Roger Brown, Hong Ni, G. Benavides, L. Yoon, K. Hyder, J. Giridhar, G. Gardner, R. D. Tyler, and K. T. Morgan
Correlation of Simultaneous Differential Gene Expression in the Blood and Heart with Known Mechanisms of Adriamycin-Induced Cardiomyopathy in the Rat
Toxicol Pathol,
June 1, 2002;
30(4):
452 - 469.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Szewczyk and L. Wojtczak
Mitochondria as a Pharmacological Target
Pharmacol. Rev.,
March 1, 2002;
54(1):
101 - 127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
