Differential paraquat uptake and redox kinetics of rat granular pneumocytes and alveolar macrophages.
Differential paraquat uptake and redox kinetics of rat granular pneumocytes and alveolar macrophages.
复制标题
大鼠颗粒性肺细胞和肺泡巨噬细胞的差异百草枯吸收和氧化还原动力学。
DOI：
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发表时间：
1982
影响因子：
3.5
通讯作者：
A. Fisher
中科院分区：
文献类型：
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作者：
H. Forman;T. Aldrich;M. Posner;A. Fisher
用离体肺细胞和灌流肺研究了细胞对百草枯（PQ）毒性敏感性差异的可能原因。测量放射性标记PQ的摄取作为时间和浓度（1 x 10（-6）-1 x 10（-3）M）的函数。对于肺泡巨噬细胞，摄取与浓度呈线性关系，但随着时间的推移，随着内部浓度接近外部浓度而达到平台期。对于颗粒状肺细胞，摄取与时间呈线性关系，但与外部浓度呈非线性关系。积累以上的外部浓度发生，并防止ATP合成的抑制剂。显然，PQ可以通过扩散进入两种细胞类型，但颗粒肺细胞也可以通过能量依赖性过程积累PQ。对于肺，摄取与时间呈非线性关系;在第1小时，当细胞内接近细胞外（1 × 10（-5）M）浓度时出现平台期，但第二个过程较慢，导致4小时累积6倍。10分钟）从细胞和肺。最大速率约高2倍（6.8 +/- 0.8 nmol/mg蛋白质）。与肺泡巨噬细胞相比，颗粒肺细胞中的Km-NADPH约为5 × 10（-6）M; Km-PQ约为2 × 10（-4）M，但估计的动力学常数相似。结果表明，PQ依赖的NADPH氧化速率会显着不同的细胞类型在低PQ浓度，因为能量依赖性运输到颗粒肺细胞，但会相当接近在高PQ浓度，扩散占主导地位。这些结论提出了一个机制的解释，如何在PQ暴露的毒性效应的差异可能会发生在一个范围内的PQ浓度。
Possible causes for differences in cellular susceptibility to paraquat (PQ) toxicity were investigated with isolated lung cells and perfused lungs. Uptake of radiolabeled PQ was measured as a function of both time and concentration (1 x 10(-6)-1 x 10(-3) M). With alveolar macrophages, uptake was linear with concentration but with time reached a plateau as internal approached external concentration. With granular pneumocytes, uptake was linear with time but nonlinear with external concentration. Accumulation above external concentration occurred and was prevented by inhibitors of ATP synthesis. Apparently, PQ can enter both cell types by diffusion, but granular pneumocytes can also accumulate PQ by an energy-dependent process. With lungs, uptake was nonlinear with time; in the 1st hr a plateau occurred when the intracellular approached extracellular (1 x 10(-5) M) concentration, but a slower second process resulted in a 6-fold accumulation by 4 hr. The effect of PQ on NADPH oxidation was measured with the supernatant fraction (12000 x g. 10 min) from cells and lungs. The maximal rate was about 2 times higher (6.8 +/- 0.8 nmol/mg of protein . min) in granular pneumocytes than in alveolar macrophages, but the estimated kinetic constants were similar (Km-NADPH approximately 5 x 10(-6) M; Km-PQ approximately 2 x 10(-4) M). The results suggest that PQ-dependent NADPH oxidation rates would differ markedly between cell types at low PQ concentration because of energy-dependent transport into granular pneumocytes but would be fairly close at high PQ concentration where diffusion predominates. These conclusions suggest a mechanistic explanation for how differences in the toxic effects of PQ exposure might occur over a range of PQ concentrations.