rapid detection of an abt-737-sensitive primed for death state in cells using microplate-based respirometry快速检测的abt - 737敏感准备在细胞死亡状态使用microplate-based呼吸运动计量法.pdfVIP

Rapid Detection of an ABT-737-Sensitive Primed for Death State in Cells Using Microplate-Based Respirometry 1 2 1 1 1 Pascaline Clerc , Gregory B. Carey , Zara Mehrabian , Michael Wei , Hyehyun Hwang , 3 4 5 1,3 Geoffrey D. Girnun , Hegang Chen , Stuart S. Martin , Brian M. Polster * 1 Department of Anesthesiology and the Shock, Trauma and Anesthesiology Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 3 Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 4 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 5 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America Abstract Cells that exhibit an absolute dependence on the anti-apoptotic BCL-2 protein for survival are termed ‘‘primed for death’’ and are killed by the BCL-2 antagonist ABT-737. Many cancers exhibit a primed phenotype, including some that are resistant to conventional chemotherapy due to high BCL-2 expression. We show here that 1) stable BCL-2 overexpression alone can induce a primed for death state and 2) that an ABT-737-induced loss of functional cytochrome c from the electron transport chain causes a reduction in maximal respiration that is readily detectable by microplate-based respirometry. Stable BCL-2 overexpression sensitiz