Clarification of Intracellular Signal Transductions in Nifedipine-Reactive Human Gingival Fibroblasts

硝苯地平反应性人牙龈成纤维细胞细胞内信号转导的澄清

• 批准号: 11671885
• 负责人: MATSUMOTO Hiroko
• 金额: $ 1.86万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671885/
• 关键词: Calcium Channel Blocker; Nifedipine; protein phosphorylation; Human Gingival Fibroblast; Gingival Overgrowth; pHi; NSAID; [Ca^<2+>]i

In order to clarify the mechanism of gingival overgrowth caused by calcium channel blockers, we have studied cellular responses in human gingival fibroblasts (hGFs) originated from nifedipine non-reactive patient (nifedipine non-responder, NIFn) and nifedipine reactive patient (nifedipine responder, NIFr).1. Effect of nifedipine on protein phosphorylationThe present study was undertaken to identify the phosphorylated protein treated with bradykinin, thapsigargin, IL-1α, or nifedipine (NIF). NIF greatly stimulated the phospholylation specifically at 35 kDa protein in hGFs. The p38 phosphorylation caused by anisomycin was greater in NIFn than that of NIFr. Because of the capability of p38 inhibiting the cell cycle, it might be possible that cell proliferation of NIFr is greater than that of NIFn.2. Effect of non-steroidal anti-inflammatory drugs (NSAIDs) on intracellular pH (pHi) and intracellular Ca^<2+> concentration ([Ca^<2+>]i)We investigated the effects of stimulants (bradykinin, histamine, thapsigargin, cyclopiazonic acid) and NSAIDs on pHi in hGFs. All of stimulants and NSAIDs lowered pHi in hGFs and Tenidap and diclofenac Na greatly induced changes in pHi. Tenidap and mefenamic acid decreased the influx of extracellular [Ca^<2+>]i evoked by TG.These results indicate the possibility that Tenidap, diclofenac Na and mefenamic acid depress gingival overgrowth.

为了阐明钙通道阻滞剂引起牙龈过度生长的机制，我们研究了硝苯地平无反应患者（硝苯地平无反应者，NIFn）和硝苯地平反应者（硝苯地平反应者， NIFr).1.硝苯地平对蛋白质磷酸化的影响本研究旨在鉴定用硝苯地平处理的磷酸化蛋白质缓激肽、毒胡萝卜素、IL-1α 或硝苯地平 (NIF) 极大地刺激了 hGF 中 35 kDa 蛋白的磷酸化，茴香霉素引起的 p38 磷酸化比 NIFr 更强。细胞周期，NIFr对细胞增殖的影响可能大于NIFn。2．非甾体抗炎药 (NSAID) 对细胞内 pH (pHi) 和细胞内 Ca^<2+> 浓度 ([Ca^<2+>]i) 我们研究了兴奋剂（缓激肽、组胺、毒胡萝卜素、环吡嗪）的影响酸）和 NSAID 对 hGF 中 pHi 的影响 所有兴奋剂和 NSAID 都会降低 hGF 以及替尼达普和双氯芬酸中的 pHi。 Na极大地诱导了pHi的变化。替尼达普和甲芬那酸减少了TG引起的细胞外[Ca^2+]i的流入。这些结果表明替尼达普、双氯芬酸钠和甲芬那酸抑制牙龈过度生长的可能性。