Monooxygenase Induction and Chlorobiphenyls in the Deep-Sea Fish Coryphaenoides armatus

Inhibition of liver microsomal ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase activities by alpha-naphthoflavone and by polyclonal antibodies to hydrocarbon-inducible cytochrome P-450E from teleost liver indicated a xenobiotic-induced origin of these activities in the deep-sea fish Coryphaenoides armatus. Specific recognition of a protein by antibodies to P-450E in an immunoblot assay further indicated xenobiotic-induced cytochrome P-450 in these animals. Levels of apparently induced cytochrome P-450 and monooxygenase activity correlated positively with the tissue content of chlorobiphenyls of known inducing activity, implicating such compounds in biochemical effects occurring in the deep ocean.     

能量限制对黄曲霉毒素B_1处理大鼠微粒体细胞色素P—450的影响

大鼠分别按自由采食(AC组)、限饲能量(RC组)、自由采食+AFB_1(黄曲霉毒素B_1,AT组)和限饲能量+AFB_1(RT组)处理16周后,检测肝微粒体Cyt P-450.结果表明:各组Cyt P-450总量变化不大:Cyt P-450_bRC组和RT组分别高于AC组和AT组(P<0.01);Cyt P-450_cRc组比AC组增加30.6％(P>0.05),RT组比AT组增加45.0％(P<0.05);微粒体酶调节的体外3~H-AFB_1与DNA结合RC和RT组分别低于AC和AT组.表明能量限制对Cyt P-450_b和Cyt p-450_c有修饰作用。能量及AFB_1-DNA结合与Cyt P-450_b和Cyt P-450_c相关性检验提示,Cyt P-450_b和Cyt P-450_c活性的提高可能是能量限制引起微粒体酶调节的3~H-AFB_1-DNA结合下降的原因之一。     

Cytochrome p-450: localization in rabbit lung

Cytochrome P-450-dependent monooxygenase systems, which metabolize endogenous as well as foriegn compounds, are found in hepatic and several extrahepatic tissues of mammals, including humans. A form of cytochrome P-450 is localized in the nonciliated bronchiolar epithelial cells (Clara cells) of the small airways of rabbit lung. The apparent high concentration of the cytochrome in this pulmonary cell type compared to liver may be an important determinant in the susceptibility of the lung to a number of toxic chemicals that undergo metabolic activation.     

Monoclonal antibody-directed radioimmunoassay detects cytochrome P-450 in human placenta and lymphocytes

A multiplicity of cytochromes P-450 is responsible for the detoxification and activation of xenobiotics such as drugs and carcinogens. Individual differences in sensitivity to these agents may reside in the cytochrome P-450 phenotype. A monoclonal antibody-directed radioimmunoassay was developed that detects epitope-specific cytochromes P-450 in human placentas and peripheral lymphocytes. Placentas from women who smoked cigarettes contained greater amounts of cytochrome P-450 with the monoclonal antibody-specific epitope than placentas from nonsmokers. The amount of this cytochrome P-450 in human peripheral lymphocytes increased after treatment of the mitogenized lymphocytes with the cytochrome P-450 inducer benz[a]anthracene.     

Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats

Cytochrome P-450-dependent metabolites of arachidonic acid (AA) increased in the kidneys of young, spontaneously hypertensive rats (SHRs) during the period of rapid elevation of blood pressure (BP) but not in adult SHRs or in Wistar Kyoto rats (WKYs) with normal BP. Treatment of SHRs and WKYs with stannous chloride (SnCl2), which selectively depletes renal cytochrome P-450, restored BP to normal, coincident with a natriuresis, in young but not in adult SHRs and did not affect either BP or sodium excretion in WKYs. Depletion of renal cytochrome P-450 was associated with decreased generation of these AA metabolites only in young SHRs. The antihypertensive effect of SnCl2 in young SHRs was greatly reduced by prevention of its cytochrome P-450-depleting action.     

Dynamics of carbon monoxide binding by heme proteins

Rebinding of carbon monoxide to myoglobin and to cytochrome P-450 after removal by a light flash occurs down to 50 degrees K for myoglobin and 25 degrees K for cytochrome P-450 in glycerol-water solution. Above 240 degrees K the reaction is second order; between 240 degrees and 200 degrees K the rebinding becomes exponential and independent of the carbon monoxide concentration. Below 150 degrees K the reaction follows a power law and is approximately 10(3) times faster for cytochrome P-450 than for myoglobin.     

Activation of 2-aminofluorene by cultured plant cells

Cultured tobacco plant cells activated 2-aminofluorene to an agent mutagenic to Salmonella typhimurium strain TA98. The plant activation of 2-aminofluorene is heat-inactivated and may not involve solely cytochrome P-450. The kinetics of activation demonstrated both time- and concentration-dependent responses.     

Cytochrome P-450--catalyzed formation of delta 4-VPA, a toxic metabolite of valproic acid

Liver damage induced by the antiepileptic drug valproic acid (VPA) is believed to be mediated by an unsaturated metabolite of the drug, delta 4-VPA. In studies of the biological origin of this hepatotoxic compound, it was found that liver microsomes from phenobarbital-treated rats catalyzed the desaturation of VPA to delta 4-VPA. Indirect evidence suggested that cytochrome P-450 was the responsible enzyme, a conclusion that was verified by studies with a purified and reconstituted form of the hemoprotein, which catalyzed the oxidation of VPA to 4- and 5-hydroxyvalproic acid and to delta 4-VPA. Desaturation of a nonactivated alkyl substituent represents a novel metabolic function of cytochrome P-450 and probably proceeds via the conversion of substrate to a transient free radical intermediate, which partitions between recombination (alcohol formation) and elimination (olefin production) pathways. These findings have broad implications with respect to the metabolic generation of olefins and may explain the increased hepatotoxic potential of VPA when it is administered in combination with potent enzyme-inducing anticonvulsants such as phenobarbital.     

Mixed function oxidase and ethanol metabolism in perfused rat liver

Oxidation-reduction changes of cytochrome P-450 and oxygen consumption were measured in isolated perfused livers from normal and phenobarbital-treated rats. Phenobarbital treatment markedly increased the aminopyrine-induced reduction of cytochrome P-450, but ethanol did not cause any redox changes of this cytochrome. It was concluded that the microsomal ethanol-oxidizing system has an insignificant role in the metabolism of ethanol in intact liver.     

Purification of an allene oxide synthase and identification of the enzyme as a cytochrome P-450

Fatty acid hydroperoxides (lipoxygenase products) are metabolized to allene oxides by a type of dehydrase that has been detected in plants, corals, and starfish oocytes. The allene oxides are unstable epoxide precursors of more complex products such as jasmonic acid, the plant growth hormone. Characterization of the dehydrase enzyme of flaxseed revealed that it is a 55-kilodalton hemoprotein. The spectral characteristics of this dehydrase revealed it to be a cytochrome P-450. It operates with the remarkable activity of greater than or equal to 1000 turnovers per second. The results establish a new catalytic activity for a cytochrome P-450 and illustrate the cooperation of different oxygenases in pathways of fatty acid metabolism.     

Carbon tetrachloride at hepatotoxic levels blocks reversibly gap junctions between rat hepatocytes

Electrical coupling and dye coupling between pairs of rat hepatocytes were reversibly reduced by brief exposure to halogenated methanes (CBrCl3, CCl4, and CHCl3). The potency of different halomethanes in uncoupling hepatocytes was comparable to their hepatotoxicity in vivo, and the rank order was the same as that of their tendency to form free radicals. The effect of carbon tetrachloride (CCl4) on hepatocytes was substantially reduced by prior treatment with SKF 525A, an inhibitor of cytochrome P-450, and by exposure to the reducing reagent beta-mercaptoethanol. Halomethane uncoupling occurred with or without extracellular calcium and did not change intracellular concentrations of calcium and hydrogen ions or the phosphorylation state of the main gap-junctional protein. Thus the uncoupling appears to depend on cytochrome P-450 oxidative metabolism in which free radicals are generated and may result from oxidation of the gap-junctional protein or of a regulatory molecule that leads to closure of gap-junctional channels. Decreases in junctional conductance may be a rapid cellular response to injury that protects healthy cells by uncoupling them from unhealthy ones.     

Effect of Pre-Soaking on Seedling Establishment and Pretilachlor Tolerance in Four Rice Genotypes

This study aimed to investigate the effects of pre-soaking for 2 h before seeding on rice seedling establishment after 15-day spraying with pretilachlor. The cytochrome P-450 content, glutathione S-transferase (GSTs), and root activity were also determined. Seedlings of four rice cultivars with contrasting tolerance of pretilachlor were compared. Seed pre-treatment by pre-soaking increased the survivability and growth under pretilachlor spray and improved seedling establishment by increasing P-450, GSTs and root activities. Tolerant genotypes, super hybrid rice, responded better to pre-soaking in direct-seeded rice treated with pretilachlor. It is important for establishment in direct-seeded rice with pre-soaking seeds before sowing in improving emergence and seedling. The positive effect of pre-soaking was proved in all four rice genotypes. Seed pre-soaking will be effective in direct-seeded rice culture to protect rice treated with pre-emergence herbicide and control weedy rice.     

南昌地区斜纹夜蛾种群的抗性水平及与两种解毒酶的关系

采用生测与生物化学的方法测定了南昌地区斜纹夜蛾种群对多类杀虫剂的抗性水平及其体内两种解毒酶(细胞色素P450单加氧酶与酯酶)的活性。结果表明,江西南昌地区的斜纹夜蛾田间种群对拟除虫菊酯类杀虫剂产生了高水平的抗性,对有机磷和氨基甲酸酯类杀虫剂产生了中等水平的抗性,而对氟虫腈、阿维菌素和氟铃脲等药剂尚未产生明显抗性。与敏感品系相比,南昌地区斜纹夜蛾种群的细胞色素P450单加氧酶和酯酶活性都有明显的提高。     

Effects of Yimu Shenghuasan Preparation on the Cytochrome P450 in Endometrial Cells and Immune Function of Dairy Cows

In order to investigate the mode of action ofYimu Shenghuasan preparation in endometrial cells of dairy cows, the primary cultured endometrial cells in cows were isolated and the inflammatory models were made by lipopolysaccharide （LPS） induction. The inflammatory cells were treated with gradient concentration of herbal medicine preparation, Yimu Shenghuasan for 48 and 72 h. The expression of cytochrome P450 （CYP450） was detected by Western blot. The amounts of IgG and lgA in sera were also detected in the endometritis of dairy cows. The expression level of CYP450 in the endometrial cells of dairy cow was increased gradually, and the amounts of IgG, IgA were increased significantly as compared with those in the control group. The expression level of CYP450 in the inflammatory cells was increased significantly in the treatment of 2 000 μg mL^-1 of Yimu Shenghuasan after 48 h of treatment.     

Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence

Induction of cytochrome P1-450 has been linked to susceptibility to certain chemically induced cancers in mouse and man. Treatment of the human cell line MCF-7 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in high levels of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (P1-450) activity. This cell line was used to isolate a human P1-450 full-length complementary DNA (cDNA) clone. The cDNA is 2566 nucleotides in length, encodes a polyadenylated messenger RNA (2.8 kilobases in length), and has a continuous reading frame producing a protein with 512 residues (molecular weight, 58,151). The human P1-450 cDNA and protein are 63 percent and 80 percent similar to mouse P1-450 cDNA and protein, respectively. Whereas the mouse TCDD-inducible P-450 gene subfamily has two members (P1-450 and P3-450), the human TCDD-inducible gene subfamily appears to have only one gene (P1-450).     

Response of Cytochrome P450 Expression to Maize Volatiles in Helicoverpa armigera (Hübner)

The 7-ethoxycoumarin O-deethylase (ECOD) activities of cytochrome P450s and differential expression of six cytochrome P450 genes induced by the volatiles from both damaged and undamaged maize plants were investigated in the cotton bollworm, Helicoverpa armigera (Hübner). The ECOD activity changed with time of exposure to maize volatiles. At 36 h after cotton bollworm larvae exposure to maize volatiles, the ECOD activities in cotton bollworm damaged and artificially damaged groups were 2.36 and 4.53 times higher than the control group respectively. The relative expression levels of CYP4S1, CYP6B2 and CYP6B7 in the cotton bollworm were significantly increased in artificially damaged plant group, which was 2.93, 5.09 and 10.66 times higher than that in the control group, respectively. The expression levels of CYP6B2, CYP6B6, CYP9A12, and CYP9A14 were much lower in the larvae exposure to volatiles from both healthy and pest damaged maize seedlings than in the control group at 12 h after larvae exposure to maize volatiles. For the cotton bollworm damaged maize group, the expression of CYP4S1 and CYP9A14 increased.