Polycyclic aromatic hydrocarbon diol epoxides increase cytosolic Ca2+ of airway epithelial cells
Polycyclic aromatic hydrocarbon diol epoxides increase cytosolic Ca2+ of airway epithelial cells
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DOI：
10.1165/ajrcmb.25.1.4405
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发表时间：
2001-07-01
影响因子：
6.4
通讯作者：
Cornfield, DN
中科院分区：
文献类型：
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作者：
Jyonouchi, H;Sun, SN;Cornfield, DN
多环芳烃(PAHs)可增加淋巴细胞和乳腺上皮细胞胞浆内钙离子浓度([Ca2+](I))，但对呼吸道上皮细胞内[Ca2+](I)的影响知之甚少。我们假设，苯并[a]芘(BP)和/或anti-7，8-dihydroxy-9，10-epoxy-7，8，9，10-tetrahydro-benzo[a]pyrene(BPDE)是一种致癌的BP代谢物，可使未转化的人小气道上皮细胞[Ca~(2+)](I)升高，并且它们对[Ca~(2+)](I)的影响与致癌性成正比。SAE[Ca~(2+)](I)用比率数字钙成像系统测定。在高钙(1 MM)和低钙(10 NM)的培养液中，BPDE在20 S内以0.2 nM的阈值浓度增加SAE[Ca~(2+)](I)。高钙组[Ca~(2+)](I)升高持续时间较长。BP和溶剂均不能改变[Ca~(2+)](I)。山茶素和1，4，5-磷酸肌醇受体(InSP(3)R)拮抗剂在低钙条件下可抑制BPDE的这种作用。我们的结论是，BPDE而不是BP增加了[Ca~(2+)](I)，部分是通过INSP(3R)从细胞液中动员Ca~(2+)来实现的。最强致癌作用的PAH二醇环氧化物在最低阈值浓度下使SAE[Ca~(2+)](I)升高，表明致癌性与PAHs对SAE[Ca~(2+)](I)的作用成正比。研究前36至48小时短期暴露于BPDE使SAE细胞对BPDE的敏感性降低，这表明BPDE也可能诱导钙信号通路的持续变化。
Polycyclic aromatic hydrocarbons (PAHs) increase cytosolic Ca2+ concentration ([Ca2+](i)) in lymphocytes and mammary epithelial cells, but little is known regarding their effects on [Ca2+](i) in airway epithelium. We hypothesized that benzo[a]pyrene (BP) and/or anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE), a carcinogenic BP metabolite, increases [Ca2+](i) in untransformed human small airway epithelial (SAE) cells and that their effects on [Ca2+](i) are directly proportional to carcinogenicity. SAE [Ca2+](i) was determined by a ratiometric digital Ca2+ imaging system. BPDE increased SAE [Ca2+](i) within 20 s in media with high (1 mM) and low (10 nM) Ca2+ at a threshold concentration of 0.2 nM. Elevation of [Ca2+](i) persisted longer with high Ca2+. Neither BP nor solvent altered [Ca2+](i). Thapsigargin and inositol 1,4 5- phosphate receptor (InsP(3)R) antagonists inhibited this BPDE action with low Ca2+. We conclude that BPDE but not BP increases [Ca2+](i) partly by mobilizing Ca2+ from cytosolic stores through an InsP(3R). The most potent carcinogenic PAH diol epoxide increased in SAE [Ca2+](i) at the lowest threshold concentration, suggesting that carcinogenicity is directly proportional to the action of PAHs on SAE [Ca2+](i). Short-term exposure to BPDE 36 to 48 h before the study rendered SAE cells less sensitive to BPDE suggesting that BPDE may also induce persistent changes in Ca2+ signaling pathways.