Characterization of calcium oscillations in normal and benzo[a]pyrene-treated clone 9 cells
Characterization of calcium oscillations in normal and benzo[a]pyrene-treated clone 9 cells
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DOI：
10.1093/toxsci/68.2.444
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发表时间：
2002-08-01
影响因子：
3.8
通讯作者：
Burghardt, RC
中科院分区：
文献类型：
--
作者：
Barhoumi, R;Mouneimne, Y;Burghardt, RC
在大鼠肝细胞系（克隆9）中分析了催产素和加压素诱导的细胞内Ca2+振荡，以确定苯并[a]芘（BaP）改变这些细胞中Ca（2+）信号模式的机制。克隆9细胞表现出最初的Ca2+峰值，随后在催产素或抗利尿素治疗后Ca2+振荡。频率范围（最大110 mHz）取决于激动剂浓度，其恒定振幅小于或等于三磷酸肌醇（InsP(3)）敏感池产生的Ca2+量。本研究研究了细胞外和细胞内池对Ca2+振荡频率的贡献，以及膜通道、第二信使和不同药理试剂在对照和bap处理细胞中对振荡频率的调节作用。结果表明，Ca2+振荡主要是由肌醇1,4,5-三磷酸（InsP(3)）敏感储存引起的，细胞外Ca2+有助于细胞内Ca2+池的再填充。Ca2+振荡的频率也受到磷脂酶C激活的蛋白激酶C的急剧影响。在bap处理的克隆9细胞中，基础Ca2+水平升高，Ca2+振荡的频率以剂量依赖性的方式被抑制。Ca2+振荡的抑制至少部分是由于BaP对K+通道开放增强的影响。这证实了四乙基氯化铵对K+通道开放的抑制可以逆转BaP对催产素诱导的Ca2+振荡的影响，并可能降低BaP的毒性。
Intracellular Ca2+ oscillations induced by oxytocin and vasopressin were analyzed in a rat liver cell line (Clone 9) in order to identify mechanisms by which benzo[a]pyrene (BaP) alters Ca(2+)signaling patterns in these cells. Clone 9 cells exhibit an initial Ca2+ spike, followed by Ca2+ oscillations upon oxytocin or vasopressin treatment. The range of frequencies (maximum 110 mHz) was dependent on agonist concentration with a constant amplitude less than or equal to the amount of Ca2+ generated from the inositol trisphosphate (InsP(3))-sensitive pool. This study examined contributions of extracellular and intracellular pools to the frequency of Ca2+ oscillations and the role of membrane channels, second messengers, and different pharmacological reagents on the regulation of oscillation frequency in both control and BaP-treated cells. Results indicated that the Ca2+ oscillations are mainly due to inositol 1,4,5-triphosphate (InsP(3))-sensitive stores and that extracellular Ca2+ contributes to refilling of this intracellular Ca2+ pool. The frequency of Ca2+ oscillations is also sharply affected by protein kinase C activated by phospholipase C. In BaP-treated Clone 9 cells, basal Ca2+ levels were elevated and the frequency of Ca2+ oscillations was suppressed in a dose-dependent fashion. Suppression of Ca2+ oscillations is due, at least in part, to an effect of BaP on enhanced opening of K+ channels. This was confirmed by showing that inhibition of the K+ channel opening by tetraethylammonium chloride can reverse the effect of BaP on oxytocin-induced Ca2+ oscillations, and potentially decrease the toxicity of BaP.