Résumé
Dihydroorotate dehydrogenase is a flavin-dependent mitochondrial enzyme to catalyze the fourth step of the de novo synthesis of pyrimidine and to oxidize dihydroorotate to orotate. By selectively inhibiting dihydroorotate dehydrogenase, thereby inhibiting pyrimidine synthesis, the enzyme has been developed for the treatment of cancer, autoimmune diseases, bacterial or viral infections, parasitic diseases and so on. The development of inhibitory drugs requires a detailed understanding of the structural characteristics and catalytic cycle mechanism of dihydroorotate dehydrogenase. Therefore, this paper reviews these two aspects, and indicates perspectives of these inhibitors in clinical application.
Sujets)
Catalyse , Mitochondries/métabolisme , Oxydoréduction , Oxidoreductases acting on CH-CH group donors/métabolismeRésumé
Objective To investigate the changes of myosin heavy chain ( MyHC) isoforms in rat masseter muscle fibers caused by chronic sleep deprivation ( CSD) and a possible link with the pathogenesis of temporomandibular joint disorders ( TMD ) .Methods Total 180 male rats were randomly divided into three groups( n=60 per group): chronic sleep deprivation group ( CSD),cage control group ( CC),and large-platform control group ( TC ) .Each group was further divided into three subgroups ( n=20 in each group)according to the observation time point(7,14,and 21 days).The expression of MyHC isoforms in mas-seter muscle fibers was investigated by real-time quantitative PCR,Western blotting and immunohistochemi-cal staining.Results The expression of MyHC-Ⅰ,MyHC-ⅡA and MyHC-ⅡB deep and shallow masseter muscle in CSD7d group had differention with the control group(MyHC-Ⅰ:(0.314±0.005,0.134±0.005, P0.05) ,and there were no differences between the CC and TC groups at any time point.Conclusion These findings suggest that CSD alters the ex-pression of MyHC isoforms,which may contribute to TMD pathogenesis.
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Objective To separate and screen components with fibrinolytic enzyme activity from twelve Chinese herbal medicines. Methods The components were extracted with water and precipitated with salt, and they were tested by fibrinolytic protein plates method. The active components with fibrinolytic activity were separated and screened which were compared with urokinase. Results Eleven of the twelve extracts showed fibrinolytic activity, while Trichosanthes kirilowii got the biggest fibrinolytic zone after 36 hours, followed by Alisma plantago-aquatica and Leonurus japonicus, and the Radix Astagali got the smallest one. According to the concentration of the protein, the area of the fibrinolytic zone and the specific activity of the components, the extract from Angelica sinensis exhibited the best specific activity at level of 48.46U/mg. Conclusion The extracts from Chinese herbal medicines except Semen Persicae exhibit fibrinolytic enzyme activity which can dissolve the fibrin in different degrees.
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Objective To observe the effects of aerobic training on plasma tissue plasminogen activator/plasminogen activator inhibitor-1 and postaglandin I2/thromboxanes A2 in rats fed a high methionine diet. Methods Ninetysix male Wistar rats were randomly divided into a normal diet control group (CR), a high methionine diet group (MR)and a high methionine diet plus 90 min aerobic training intervention group (T + MR). After 8 weeks of training, the plasma level of homocysteine (Hcy) 6-keto-PGF1α, TXB2, t-PA and PAI-1 were measured. Results Plasma Hcy in the MR group increased two-fold as compared with the CR group, whereas t-PA/PAI-1 and 6-keto-PGF1α/TXB2 of the MR group decreased significantly. Plasma Hcy in the T + MR group significantly decreased, while plasma t-PA/PAI-1 and 6-ketoPGF1α/TXB2 increased significantly compared with the MR group. The above parameters were not different in the T + MR group from those of the CR group. Conclusions Hyperhomocysteinemia could be induced by a high methionine diet.Proper training can decrease the plasma Hcy level of rats fed with a high methionine diet, and correcting the imbalance of t-PA/PAI-1 and 6-Keto-PGF1α/TXB2 could prevent the development of hyperhomocysteinemia.
Résumé
Objective To evaluate the diagnostic value of surface enhanced laser desorption/ionization time of flight mass spectrom-etry(SELDI-TOF-MS) for Paget disease. Methods The relative contents of serum proteins of 15 healthy people,15 patients with chronic eczema and 20 patients with Paget were detected by Weak cation exchanger protein chip (WCx2) and SELDI-TOF-MS. Results The con-tents of two proteins (3868Da,8876Da) had significant difference in healthy people and Paget disease patients(P<0.01). 291IDa, 3868Da and 5097Da protein peaks had significant difference in chronic eczema and Paget disease(P<0.05). Conclusion It shows great potentiality for early diagnosis and screening the tumor biomarkers of Paget disease with SELDI-TOF-MS.