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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제20권 제4호
- 발행연도
- 2016.7
- 수록면
- 367 - 378 (12page)
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초록· 키워드
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Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their ρ0 cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration.
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참고문헌 (29)
참고문헌 신청
Basu A / 2010 / Cellular responses to Cisplatin-induced DNA damage / J Nucleic Acids
Miller RP / 2010 / Mechanisms of Cisplatin nephrotoxicity / Toxins(Basel) 2:2490~2518
Kohno K / 2015 / Mitochondrial transcription factor A and mitochondrial genome as molecular targets for Cisplatin-based cancer chemotherapy / Int J Mol Sci 16:19836~19850
Budihardjo I / 1999 / Biochemical pathways of caspase activation during apoptosis / Annu Rev Cell Dev Biol 15:269~290
Chen M / 2002 / Initiator caspases in apoptosis signaling pathways / Apoptosis 7:313~319
Miller RP / 2010 / Mechanisms of Cisplatin nephrotoxicity / Toxins(Basel) 2:2490~2518
Kohno K / 2015 / Mitochondrial transcription factor A and mitochondrial genome as molecular targets for Cisplatin-based cancer chemotherapy / Int J Mol Sci 16:19836~19850
Budihardjo I / 1999 / Biochemical pathways of caspase activation during apoptosis / Annu Rev Cell Dev Biol 15:269~290
Chen M / 2002 / Initiator caspases in apoptosis signaling pathways / Apoptosis 7:313~319
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