Radiation protects adriamycin-induced apoptosis |
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| Authors: | Chae Han-Jung Kim Hyung-Ryong Lee Wan-Goo Kwak Yong-Keun Kim Woo-Hyun Hong Seong-Tshool Cho Gwang-Hyun Kim Jung-Soo Chae Soo-Wan |
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| Affiliation: | a Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jeonju, Republic of Koreab Department of Dental Pharmacology and Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University, Jeonju, Republic of Koreac Department of Biochemistry, School of Medicine, Chonbuk National University, Jeonju, Republic of Koread Department of Microbiology, School of Medicine, Chonbuk National University, Jeonju, Republic of Koreae Department of Psychiatry, Chonbuk National University Hospital, Jeonju, Republic of Koreaf Department of Radiation Oncology, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea |
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| Abstract: | Combined radiotherapy and chemotherapy have represented major advance in the therapeutic management of cancer therapy. Anthracycline antineoplastic agents are limited by a high incidence of severe and usually irreversible cardiac toxicity, the cause of which remains controversial. When the primary cardiomyocytes isolated from neonatal rats were preirradiated by γ-ray, the cells were highly resistant to adriamycin-induced apoptosis. This study shows that irradiation inhibited apoptosis by enhancing Bcl-2, attenuating Bax induction, and preventing collapse of mitochondrial membrane potential (ΔΨ), cytochrome c release into cytoplasm and caspase-3, -6 and -9 activations.
In addition, the preirradiation stimulated the activity of manganese-superoxide dismutase (Mn-SOD) and the expression of Mn-SOD mRNA and protein. Adriamycin decreased Mn-SOD activity but did not change the activity of copper/zinc (Cu/Zn)-SOD under either pre- or nonirradiated condition. Phosphothioate-linked antisense against Mn-SOD, which specifically knocked down the activity of Mn-SOD but not that of Cu/Zn-SOD, reversed irradiation-induced protective effect in adriamycin-exposed cardiomyocytes. These data suggest that the irradiation-induced expression of Mn-SOD plays an important role in irradiation-mediated protection in adriamycin-exposed rat ventricular cardiomyocytes. |
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| Keywords: | Adriamycin Copper Manganese superoxide dismutase Mitochondrial membrane potential Reactive oxygen species Superoxide dismutase Zinc-superoxide dismutase |
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