title: Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-κB translocation and ROS production in synoviocytes.
abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca(2+) entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca(2+) entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca(2+) release from intracellular stores. The nuclear translocation of NF-κB was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-κB. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca(2+) mobilization, activating NF-κB nuclear translocation and depressing ROS production.
authors: Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071, PR China.
authors: Fen
authors: F
authors: Hu
authors: Shuang
authors: S
authors: Yang
authors: Dan
authors: D
authors: Zhao
authors: Shuyan
authors: S
authors: Zhu
authors: Yuxiang
authors: Y
authors: Wang
authors: Junying
authors: J
authors: Li
mesh_terms: D000143:Acids; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D000143:Acids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D054801:Phosphoinositide Phospholipase C; D002211:Capsaicin; D002118:Calcium