TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization
- Department of Biophysics, School of Physics, Ministry of Education Key Laboratory of Bioactive Materials, Nankai University, 94 Weijin Road, Nankai District, Tianjin 300071 (China)
- Institute of Cell Biology, Beijing Normal University, Beijing 100875 (China)
Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca{sup 2+}]{sub c}) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca{sup 2+}]{sub c} and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca{sup 2+}]{sub c} elevation, ROS production, and mitochondrial membrane depolarization.
- OSTI ID:
- 21143673
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 369, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2008.02.155; PII: S0006-291X(08)00363-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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