ABSTRACT
Cytochrome P450 enzymes participate in the biotransformation of various organic compounds in living organisms. Cytochrome P450 enzymes are present and active in various brain regions, which mediate the synthesis and metabolism of various endogenous substances in the brain, so the enzymes play an important role in maintaining homeostasis of the central nervous system. And cytochrome P450 enzymes in brain are widely involved in metabolism of central drugs such as tramadol, so the changes of their activities or expressions may affect the drug's efficacy in brain. In addition, in view of the important roles of cytochrome P450 enzymes in the biotransformation of endogenous and exogenous substances in brain, the importance of their genetic polymorphism or activity changes in neuropsychiatric diseases is being gradually described. Therefore, in order to provide theoretical basis for the development of related targeted therapeutic drugs and explore whether cytochrome P450 enzymes in the brain can be used as therapeutic targets for central diseases, the development in the function of cytochrome P450 enzymes in brain and their recent advances in neuropsychiatric diseases by reviewing the relevant research in recent years are summarized.
ABSTRACT
Cytochrome P450 1A (CYP1A), one of the major CYP subfamily in humans, not only metabolizes xenobiotics including clinical drugs and pollutants in the environment, but also mediates the biotransformation of important endogenous substances. In particular, some single nucleotide polymorphisms (SNPs) for genes may affect the metabolic ability of endogenous substances, leading to some physiological or pathological changes in humans. This review first summarizes the metabolism of endogenous substances by CYP1A, and then introduces the research progress of SNPs, especially the research related to human diseases. Finally, the relationship between SNPs and diseases is discussed. In addition, potential animal models for gene editing are summarized. In conclusion, CYP1A plays an important role in maintaining the health in the body.
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With the rapid development of high-sensitivity detection methods, stable isotope tracing technique has received increasing attention. Stable isotope tracing technique can accurately track the activity of labeled compounds in the body through the tracer atoms and determine their specific metabolic pathways based on the distribution of isotopic peaks of the intermediate metabolites. By calculating the flux, the metabolic pathways are analyzed to provide a basis for the study of disease mechanism and drug metabolism. In recent years, the technique has a wide application in the field of biomedicine. This paper summarizes the applications of stable isotopic tracer technique in the metabolic regulation of endogenous substances such as carbohydrate metabolism, lipid metabolism, amino acid metabolism, hormone metabolism, nucleic acid metabolism, and so on.
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Cytochrome P450 (CYP450) is a superfamily of heme-thiolate proteins, which is involved in the metabolism and activation of various endogenous and exogenous substances, including food, drugs and pollutants. Previous studies of the CYP450 genes mainly focused on their function in drug metabolism. However, in recent years, studies have found that CYP450 are also involved in the development and progression of various diseases, including Parkinson's disease (PD), cancer, cardiomyopathy and heart failure (HF). By far, the process and related mechanisms of CYP450 in the metabolism of endogenous substances in brain tissues has not been clarified yet. In this paper, we summarized the research progress of CYP450 genes involved in the metabolism of endogenous substances, in order to provide a new idea for the exploration of the functions of CYP450 genes expressed in the brain.
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@#To establish a simple and sensitive LC-MS/MS method for simultaneous determination of the concentration for L-tryptophan(L-Try)and L-kynurenine(L-Kyn)in rat plasma. The changesin the process of the liver tumors formation may provide a basis for the diagnosis of liver cancer. 3-Nitro-L-tyrosine(3-NT)were added as the internal standard for the determination of two active substances and the chromatographic analysis was performed on a RRHD Eclipse Plus C18 column(3. 0 mm×100 mm, 1. 8 μm). The mobile phase was composed of water and acetonitrile(containing 0. 1%formic acid)(90 ∶10)at a flow rate of 0. 25 mL/min, and the injection volume is 5 μL. Detection and quantification were performed by mass spectrometry in multiple reaction monitoring mode with m/z 205. 12→146. 10(L-Try), m/z 209. 09 →146. 10(L-Kyn), m/z 227. 09→181. 10(3-NT), respectively. The results show that thelinear ranges were 9. 670-9 670 ng/mL for L-Try, and 9. 973-9973 ng/mL for L-Kyn(r2≥0. 9990). The limit of quantitation were 9. 670 ng/mL for L-Try, and 9. 973 ng/mL for L-Kyn, respectively. The intra- and inter-day precisions were all less than15%; the recoveries ofthe two analytes were more than 81. 17% and severe matrix effect was not observed. The ratio of L-Try/L-Kyn determined by LC-MS/MS in rat plasma showed an overall downward trend, which could used effectively for the drug metabolism studies and researches on the action mechanism of medicine on liver cancer. A rapid, simple, sensitive and specific LC-MS/MS method has been successfully developed and could also be used effectively for the drug metabolism studies and researches on the action mechanism of medicine on liver cancer.
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Objective To observe the expression of ghrelin and growth hormone secretagogue receptor (GHSR) in pancreas of rats with acute necrotizing pancreatitis (ANP),and investigate the role of ghrelin in the pathogenesis of ANP.Methods Seventy SD rats were randomly divided into ANP group (n =35) and control group (n =35).ANP model was induced by retrograde injection of 4％ sodium taurocholate into the biliary and pancreatic duct.Rats in the control group underwent laparotomy with gentle pancreas manipulation only.At 3,6,12,24,48 h after ANP induction,the rats were sacrificed,and the serum level of amylase was determined,pathological changes in pancreatic tissue were routinely observed and scored.The expressions of ghrelin mRNA,protein and GHSR mRNA,protein in pancreas were evaluated by RT-PCR and Western blot.Results Serum amylase level began to increase at 3h after sodium taurocholate injection and reached the peak value at 6 h [(8244 ± 2950) U/L],which was significantly higher than that in control group (P ＜ 0.05).Pancreatic injuries was aggravated with time,the pathologic score at 24 h was (11.91 ± 1.31) score,which was significantly higher than (3.12 ± 1.60) score in the control group.The expressions of ghrelin mRNA and GHSR mRNA in pancreas of ANP group were increased gradually with time,and were significantly higher than those of control group at all time points,at 48 h,1.29 ±0.64 vs 0.58 ±0.05 and 0.94 ±0.16vs 0.19 ±0.03,P ＜ 0.05.The expressions of ghrelin protein and GHSR protein in pancreas of ANP group were significantly higher than that in control group at 12,24,48 h.at 48 h,3.05 ± 0.48 vs 2.18 ± 0.23 and 2.34 ± 0.32 vs 1.55 ± 0.10 (P ＜ 0.05).Conclusions The expressions of ghrelin mRNA,protein and GHSR mRNA,protein of pancreas are significantly increased in rats of ANP,and are associated with the severity of ANP.
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AIM: To observe the alteration of urotensin II (UII) receptors and contractile response to UII in rat aorta after balloon angioplasty injury. METHODS: The plasma membrane isolated from balloon injured aorta was used to study the binding of [ 125 I]-UII to the membrane and the contractile potency of UII on rat aorta was assayed. RESULTS: In contrast to the normal aorta, the contractile potency to UII enhanced in balloon injury artery and the calculated maximal number of specific binding sites (Bmax) was increased about 44% and 36% respectively in rat artery after balloon injury 3 and 21 days ( P