Unbiased compound screening with a reporter gene assay highlights the role of p13 in the cardiac cellular stress response |
| |
| Authors: | Naoki Inoue Taisei Hirouchi Atsushi Kasai Shintaro Higashi Natsumi Hiraki Shota Tanaka Takanobu Nakazawa Kazuto Nunomura Bangzhong Lin Akiko Omori Atsuko Hayata-Takano Yoon-Jeong Kim Takefumi Doi Akemichi Baba Hitoshi Hashimoto Norihito Shintani |
| |
| Institution: | 1. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan;3. Research Fellow of the Japan Society for the Promotion of Science, Japan;4. Department of Pharmacology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan;5. Office for University–Industry Collaboration, Osaka University, Osaka 565-0871, Japan;6. Compound Library Screening Center Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan;g. Department of Biology, University of Padua, 35121 Padua, Italy;h. Molecular Research Center for Children''s Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;i. Laboratory of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan;j. Faculty of Pharmaceutical Sciences, Hyogo University of Health Science, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan;k. Division of Bioscience, Institute for Datability Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan |
| |
| Abstract: | We recently showed that a 13-kDa protein (p13), the homolog protein of formation of mitochondrial complex V assembly factor 1 in yeast, acts as a potential protective factor in pancreatic islets under diabetes. Here, we aimed to identify known compounds regulating p13 mRNA expression to obtain therapeutic insight into the cellular stress response. A luciferase reporter system was developed using the putative promoter region of the human p13 gene. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1α, a master player regulating mitochondrial metabolism, increased both reporter activity and p13 expression. Following unbiased screening with 2320 known compounds in HeLa cells, 12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that elicited >2-fold changes in p13 mRNA expression were identified. Among them, four cardiac glycosides decreased p13 expression and concomitantly elevated cellular oxidative stress. Additional database analyses showed highest p13 expression in heart, with typically decreased expression in cardiac disease. Accordingly, our results illustrate the usefulness of unbiased compound screening as a method for identifying novel functional roles of unfamiliar genes. Our findings also highlight the importance of p13 in the cellular stress response in heart. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
