Effects of furanocoumarins from apiaceous vegetables on the catalytic activity of recombinant human cytochrome P-450 1A2.
Effects of furanocoumarins from apiaceous vegetables on the catalytic activity of recombinant human cytochrome P-450 1A2.
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DOI：
10.1007/s10930-011-9350-0
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Peterson S
中科院分区：
文献类型：
--
作者：
Kang AY;Young LR;Dingfelder C;Peterson S
抑制细胞色素P-450 1A 2（CYP 1A 2）介导的前致癌物活化可能是一个重要的化学预防机制。食用芹菜（富含呋喃香豆素）会抑制人类的CYP 1A 2。由于许多呋喃香豆素类化合物是几种酶的有效抑制剂，我们研究了三种来自芹菜的呋喃香豆素类化合物对人CYP 1A 2（hCYP 1A 2）的影响。我们使用来自表达hCYP 1A 2的酿酒酵母的微粒体评估hCYP 1A 2甲氧基试卤灵O-脱甲基酶（MROD）活性。异茴芹素对hCYP 1A 2表现出基于机制的失活（MBI）（Ki = 1.2 μM，kinact = 0.34 min−1，分配比= 8）。Imperatorin和trioxsalen被表征为混合抑制剂，Ki值分别为0.007和0.10 μM。这些结果表明，即使存在于低水平的芹菜，欧前胡素，trioxsalen和isopimpinellin可能会显着促进CYP 1A 2抑制和潜在的降低原致癌物的激活。此外，与可逆抑制剂相比，异茴芹素对CYP 1A 2的体内作用可能更持久。
Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are potent inhibitors of several CYP, we characterized the effects of three furanocoumarins from apiaceous vegetables on human CYP1A2 (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin exhibited mechanism-based inactivation (MBI) of hCYP1A2 (Ki = 1.2 μM, kinact = 0.34 min−1, and partition ratio = 8). Imperatorin and trioxsalen were characterized as mixed inhibitors with Ki values of 0.007 and 0.10 μM, respectively. These results indicate that even if present at low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition and potentially decreased procarcinogen activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be longer lasting compared to reversible inhibitors.
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影响因子：
4.1
作者：
CAI, YN;BENNETT, D;DIGIOVANNI, J
通讯作者：
DIGIOVANNI, J
影响因子：
3.9
作者：
Draper, AJ;Madan, A;Parkinson, A
通讯作者：
Parkinson, A
影响因子：
4.7
作者：
Kleiner, HE;Vulimiri, SV;DiGiovanni, J
通讯作者：
DiGiovanni, J
影响因子：
4.1
作者：
KUNZE, KL;TRAGER, WF
通讯作者：
TRAGER, WF
影响因子：
1.8
作者：
CLARKE, SE;AYRTON, AD;CHENERY, RJ
通讯作者：
CHENERY, RJ