differential mitochondrial toxicity screening and multi-parametric data analysis微分的线粒体毒性筛选和不确定型数据分析.pdfVIP

Differential Mitochondrial Toxicity Screening and Multi- Parametric Data Analysis 1 3 1 1 2 Maria V. Tsiper , Jennifer Sturgis , Larisa V. Avramova , Shilpa Parakh , Raymond Fatig , Ana Juan- ´ 3 5 1 5 5 3,4 Garcıa , Nianyu Li , Bartek Rajwa , Padma Narayanan , C. W. Qualls, Jr. , J. Paul Robinson , V. Jo Davisson2* 1 Bindley Bioscience Center at Purdue University Discovery Park, West Lafayette, Indiana, United States of America, 2 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, United States of America, 3 Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, United States of America, 4 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America, 5 Comparative Biology and Safety Sciences, Amgen Inc, Seattle, Washington, United States of America Abstract Early evaluation of new drug entities for their potential to cause mitochondrial dysfunction is becoming an important task for drug development. Multi-parametric high-content screening (mp-HCS) of mitochondrial toxicity holds promise as a lead in-vitro strategy for drug testing and safety evaluations. In this study, we have developed a mp-HCS and multi-parametric data analysis scheme for assessing cell responses to induced mitochondrial perturbation. The mp-HCS measurements are shown to be robust enough to allow for quantitative comparison of biological systems with different metabolic pathways simulated by alteration of growth media. Substitution of medium glucose for galactose sensitized cells to drug actio