JNK and p38 MAPK are independently involved in tributyltin-mediated cell death in rainbow trout (Oncorhynchus mykiss) RTG-2 cells |
| |
| Authors: | Noriko Urushibara Shinya Mitsuhashi Tomoyuki Sasaki Hisae Kasai Mamoru Yoshimizu Hiroyoshi Fujita Atsushi Oda |
| |
| Institution: | 1. Faculty of Fisheries Sciences, Hokkaido University, Hakodate 041-8611, Japan;2. Laboratory of Environmental Biology, Department of Preventive Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan;3. Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8638, Japan;1. Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Lucknow 226001, India;2. Department of Biochemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India;1. Université de Lyon, UMR LEHNA 5023, F-69100, Villeurbanne, France;2. INRA, USC IGH 1369, ENTPE, F-69518, Vaulx-en-Velin, France;1. Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Crta. de la Coruña, km. 7, 5, 28040 Madrid, Spain;2. Département d’Ecologie et Génie de l’Environnement., Faculté des Sciences de la Nature et de la Vie et Sciences de la Terre et de l’Univers, Université 08, Mai 1945 Guelma, BP 401, 24000 Guelma, Algeria;3. Laboratoire de Biotechnologie, Environnement et Santé, Université Mohammed Seddik Benyahya, Jijel, BP 98, Ouled Aissa, Jijel 18000, Algeria;4. Laboratoire de Pharmacologie et Phytochimie, Université Mohammed Seddik Benyahya, Jijel, BP 98, Ouled Aissa, Jijel 18000, Algeria;1. Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK;2. Division of Fisheries, Department of Agricultural Technology, Faculty of Technology, Mahasarakham University, Khamriang Sub-District, Kantarawichai, Mahasarakham, 44150, Thailand;3. Elanco Canada Ltd., Aquaculture Research and Development, P.O. Box 17, Victoria, P.E., C0A 2G0, Canada;4. SEPPIC, 22 Terrasse Bellini, Paris La Défense, 92806 Puteaux, France |
| |
| Abstract: | Mitogen-activated protein kinases (MAPKs) are a family of Ser/Thr protein kinases that transmit various extracellular signals to the nucleus inducing gene expression, cell proliferation, and apoptosis. Recent studies have revealed that organotin compounds induce apoptosis and MAPK phosphorylation/activation in mammal cells. In this study, we elucidated the cytotoxic mechanism of tributyltin (TBT), a representative organotin compound, in rainbow trout (Oncorhynchus mykiss) RTG-2 cells. TBT treatment resulted in significant caspase activation, characteristic morphological changes, DNA fragmentation, and consequent apoptotic cell death in RTG-2 cells. TBT exposure induced the rapid and sustained accumulation of phosphorylated MAPKs, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase (p38 MAPK). Further analysis using pharmacological inhibitors against caspases and MAPKs showed that TBT also induced cell death in a caspase-independent manner and that p38 MAPK is involved in TBT-induced caspase-independent cell death, whereas JNK is involved in the caspase-dependent apoptotic pathway. Thus, TBT employs at least two independent signaling cascades to mediate cell death in RTG-2 cells. To our knowledge, this is the first study revealing the relationship between MAPK activation and TBT cytotoxicity in RTG-2 cells. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
