Induction of microsomal aryl hydrocarbon (3,4-benzo(alpha)pyrene) hydroxylase and cytochrome P-450K in rat kidney cortex. II. Interactions with the induced hemoprotein.
Induction of microsomal aryl hydrocarbon (3,4-benzo(alpha)pyrene) hydroxylase and cytochrome P-450K in rat kidney cortex. II. Interactions with the induced hemoprotein.
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大鼠肾皮质中微粒体芳烃（3,4-苯并（α）芘）羟化酶和细胞色素 P-450K 的诱导。
DOI：
10.1016/0003-9861(73)90548-1
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发表时间：
1973
影响因子：
3.9
通讯作者：
D. L. Cinti
中科院分区：
文献类型：
--
作者：
S. Jakobsson;R. Grundin;H. Thor;D. L. Cinti
苯并（α）芘处理只刺激大鼠肾皮质微粒体细胞色素P-450 K和苯并（α）芘羟化酶活性。细胞色素P-450 K的光谱特性表明，苯并（α）芘处理的大鼠还原血红素蛋白CO-复合物的452 nm峰没有发生位移。氧化型细胞色素P-450 K的非平衡绝对光谱在414 nm处显示最大吸收，在385 nm处显示另一个带，在398 nm处显示明显的肩。向肾微粒体中加入苯并（α）芘导致仅在苯并（α）芘处理的大鼠中观察到的I型光谱变化。在对照大鼠的连二亚硫酸盐处理的微粒体中加入异氰化乙酯，在432 nm和458 nm处产生两个Soret峰。在苯并（α）芘处理的大鼠中，这些峰成比例地增加;此外，458 nm峰没有移动。两个峰的相对高度处于pH依赖性平衡，与肝脏中观察到的相似;然而，与肝脏相反，苯并（α）芘处理和对照微粒体的pH（峰高比等于1）相同。这些数据表明，新诱导的血红素蛋白的光谱特性显着不同的苯并（α）芘诱导的肝血红素蛋白，但类似于“非诱导”肾血红素蛋白。芳基羟化酶系统抑制剂α-萘酚酮引起Ⅰ型光谱变化，提示α-萘酚酮的作用方式可能是在活性部位或附近与细胞色素P-450 K相互作用。最后，细胞色素P-450 K的还原速率不受苯并（α）芘的影响。
Benzo(α)pyrene treatment resulted in stimulation of only cytochrome P-450Kand benzo(α)pyrene hydroxylase activity in rat kidney cortex microsomes. Spectral properties of cytochrome P-450Kshowed that the 452 nm peak of the reduced hemoprotein CO-complex was not shifted in benzo(α)pyrene-treated rats. The off-balance absolute spectrum of oxidized cytochrome P-450Kdisplayed an absorption maximum at 414 nm, another band at 385 nm, and a distinct shoulder at 398 nm. Addition of benzo(α)pyrene to kidney microsomes resulted in a type I spectral change seen only in benzo(α)pyrene-treated rats. The addition of ethyl isocyanide to dithionitetreated microsomes from control rats gave rise to two Soret peaks, 432 nm and 458 nm. These peaks were proportionately increased in benzo(α)pyrene-treated rats; furthermore, the 458 nm peak was not shifted. The relative heights of the two peaks were in a pH-dependent equilibrium similar to that observed in liver; however, in contrast to liver, the pH, at which the ratio of the peak heights equals one, was the same for both benzo(α)pyrene-treated and control microsomes. These data indicate that the newly induced hemoprotein has spectral properties markedly different from those of the benzo(α)pyrene-induced liver hemoprotein, yet similar to those of the “noninduced” kidney hemoprotein. α-Naphthoflavone, an inhibitor of the aryl hydroxylase system, induced a type I spectral change, suggesting the mode of action of α-naphthoflavone to be its interaction with cytochrome P-450Kprobably at or near the active site. Finally, the rate of reduction of cytochrome P-450Kwas not affected by the presence of benzo(α)pyrene.