Rapid increases in inositol trisphosphate and intracellular Ca++ after heat shock |
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| Authors: | M A Stevenson S K Calderwood G M Hahn |
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| Affiliation: | 3. National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan;4. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, 101-0062, Japan;5. AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo 162-8655, Japan;6. AIDS Research Centre, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;12. Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan;8. Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892-1868;1. Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China;2. The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, PR China;3. Department of Infectious Disease, Guangzhou No. 8 People''s Hospital, Guangzhou 510060, PR China;1. Chemical Diversity Research Institute, Rabochaya St. 2a, Khimki, Moscow Region, 141401, Russia;2. ChemDiv, 6605 Nancy Ridge Drive, San Diego, CA, 92121, United States;3. Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Ufa, Russia;4. Viriom Inc, 12760 High Bluff Drive, St 370, San Diego, CA, 92130, United States;5. Avisa Pharmaceuticals LLC, 1835 E. Hallandale Beach Blvd, #442, Hallandale Beach, Fl, 33009, United States;1. College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming 650500, PR China;2. Central Laboratory, The NO. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming 650021, PR China;1. Dipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy;2. Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, via Giorgieri, 1, 34127 Trieste, Italy |
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| Abstract: | Heat shock (45 degrees C) caused a rapid (less than 1 min) release of inositol trisphosphate from the membranes of HA-1 CHO fibroblasts. The rise in inositol trisphosphate concentration was followed by an increase in intracellular free Ca++. In addition to the heat induced rise in intracellular free Ca++, we observed an increase in 45Ca++ influx following nonlethal heat shock (45 degrees C/10 min). The heat-induced increase in 45Ca++ influx was linearly related to membrane accumulation of phosphatidic acid, phosphoinositide metabolite that may be involved in Ca++ gating. These results suggest that the membrane may be the proximal target of heat shock; stimulation of rapid breakdown of polyphosphoinositides and subsequent increases in intracellular free Ca++ may provide a mechanistic insight into the pleiotropic effects of heat. In addition, the large increases in Ca++ influx could initiate a Ca++ dependent mechanism of thermal cell killing. |
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