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51.
Hydroxylation of p-chlorotoluene with heminthiol complexes, Fenton's system and Udenfriend's system was studied and the complexes assessed as models of cytochrome P-450 monooxygenases. Five species of possible hydroxylation products of p-chlorotoluene, namely, p-chlorobenzyl alcohol, 2-chloro-5-methylphenol, p-chlorobenzaldehyde, 4-chloro-2-methylphenol and 5-chloro-2-methylphenol, were studied using high performance liquid chromatography. The oxidation reactions were characterized by the yields of hydroxylation products and the product ratio. The system consisting of hemin and cysteine ethyl ester as well as Udenfriend's system gave relatively high hydroxylation yields and the former only induced a methyl migration during hydroxylation (methyl NIH shift). However, neither Fenton's nor Udenfriend's systems induced a methyl NIH shift. The hemin-thiol complex is thus concluded to be a good chemical model of cytochrome P-450 monooxygenases. 相似文献
52.
Nishizawa R Nishiyama T Hisaichi K Matsunaga N Minamoto C Habashita H Takaoka Y Toda M Shibayama S Tada H Sagawa K Fukushima D Maeda K Mitsuya H 《Bioorganic & medicinal chemistry letters》2007,17(3):727-731
Hydroxylated derivatives were designed and synthesized based on the information of oxidative metabolites. Compounds derived from beta-substituted (2R,3R)-2-amino-3-hydroxypropionic acid showed improved inhibitory activities against the binding of MIP-1alpha to human CCR5, compared with the non-hydroxylated derivatives and the other isomers. 相似文献
53.
CYP2E1 is known to be induced in streptozotocin (STZ)-treated diabetic rats (STZ rats), and its induction is improved by insulin. We have examined the age-dependent changes of CYP2E1 in the liver microsomes of type 1 diabetic STZ rats, the effects of VOSO4 on the contents of total P450 and CYP2E1, and the activities of CYP2E1 in terms of p-nitrophenol hydroxylation. The contents of P450 and CYP2E1 and CYP2E1 activity were enhanced with the development of diabetes. When the hyperglycemia of STZ rats was improved by daily intraperitoneal injections of VOSO4 for 10 days at the doses of 7 mg/kg body weight for 5 days, 5 mg/kg for the following 3 days, and then 2.5 mg/kg for 2 days, the P450 and CYP2E1 levels and CYP2E1 activity were lowered than those in the untreated STZ rats. To understand the mechanism underlying CYP2E1-dependent hydroxylation activity, the production of reactive oxygen species was examined in the NADPH-liver microsomal systems by ESR spin-trapping. Singlet oxygen (1O2) was detected in all microsomal systems, while superoxide anion radical(*O2-) and hydroxyl radical (*OH) were not. On the basis of these results, we conclude that (1) CYP2E1 level and activity are enhanced in the diabetic state, however, they are improved by VOSO4 treatment, and (2) 1O2 is generated during CYP2E1-dependent substrate oxygenation. 相似文献
54.
The full-length cDNA that encodes the hemolytic toxin Avt-I, with 226 amino acids, from the venomous sea anemone Actineria villosa has been cloned using the oligo-capping method. The cDNA contains 681bp open reading frame and its predicted amino acid sequences revealed that Avt-I was basic polypeptides without cysteine residues and Arg-Gly-Asp (RGD) motif sequence. The mature Avt-I has a predicted molecular weight of 19.6 kDa and its theoretical isoelectric point is 9.3. The Avt-I revealed 99, 61, 57, and 57% amino acid similarity with hemolytic toxins Pstx20, EqtII, StII, and HmT from Phyllodiscus semoni, Actinia Equina, Stichodactyla helianthus, and Heteractis magnifica, respectively. The characteristic amphiphilic alpha-helix structure was found at the N-terminal region of the mature Avt-I. Recombinant Avt-I (rAvt-I) was expressed in Escherichia coli BL21 (DE3) strain as a biologically active form and purified rAvt-I caused 50% hemolytic activity against 1% sheep erythrocytes at a concentration of 6.3 ng/ml (0.32 nM). M9Y medium led to more than 2-fold increase in rAvt-I yield than cultivation in Luria-Bertani medium. 相似文献
55.
本研究在山东省开展了脊髓灰质炎病毒(Poliovirus,PV)的外环境监测,从济南、临沂两地采集污水标本,浓缩处理后进行病毒分离,对分离到的PV采用中和试验进行血清定型,并对其VP1及3D区进行序列测定,分析其基因突变和重组情况。2010年,共采集污水标本32份,PV阳性10份,阳性率31.3%;分离到18株PV(PV1型3株,PV2型9株,PV3型6株),均为疫苗相关株,VP1完整编码区核苷酸变异数在0~4个之间,在3株PV2型病毒和4株PV3型病毒的基因组中发现重组;对VP1区影响神经毒力的减毒位点分析发现,PV1型病毒中有1株在nt 2 749发生突变(A→G),PV2型病毒中有1株在nt2 908发生A→G突变,3株在nt2 909发生U→C突变,6株PV3型病毒全部在nt2 493发生C→U突变。环境污水中可以分离到PV,其基因重组率和主要减毒位点的回复突变率较高,未发现脊灰野毒株和疫苗衍生株脊灰病毒(Vaccine-derived poliovirus,VDPV)。 相似文献
56.
Observed localization of the long-term cultured rat adherent natural killer cells in mammary tumor tissues 总被引:2,自引:0,他引:2
Adherent natural killer (A-NK) cells were isolated from splenic lymphocytes and treated with long-term culture in the presence
of recombinant interleukin-2 (rIL-2). Immunocytochemical and flow-cytometric analysis revealed that most of the A-NK cells
strongly expressed lymphocyte-function-associated antigen 1 (LFA-1α, and LFA-1β) throughout the incubation. All A-NK cells
from 8- to 150-day cultures, particularly those cultured for 8 days, showed significant cytolytic activity against all targets.
Analysis of the tissue distribution of the injected [3H] uridine-labeled A-NK cells demonstrated that, in the first 3 h, most (over 60%) cells localized in the lungs, and that
most cells remained temporally within the cavities of blood capillaries of the lungs and moved gradually into lymphoid and
other tissues. Peritumoral injection of various kinds of adjuvant, particularly Freund's complete adjuvant (FCA) plus bacillus
Calmetee-Guérin (BCG), resulted in a marked accumulation of [3H]A-NK cells in mammary tumor tissues 24 h after injection, and simultaneously in the formation of vessels resembling high-endothelium
venules (HEV), infiltration of LFA-1+ lymphocytes and expression of the ICAM-1 molecule on the tumor cells in the sites of tumor tissues. When 30 × 106 A-NK cells were intravenously administered, significant retardation of tumor growth and prolongation of survival of tumor-bearing
rats were observed in the groups that received the prior injection of adjuvants, especially FCA + BCG and Freund's incomplete
adjuvant (FIA) + BCG. The suppressive effect of combination therapy on tumor growth was blocked effectively by the injection
of anti-ICAM-1 mAb. These results indicate that the prior injection of proper adjuvant into the peritumoral region is effective
for the selective accumulation or infiltration of A-NK cells into the sites of tumor tissues, and results in the marked retardation
of tumor growth.
Received: 18 May 1999 / Accepted: 4 October 1999 相似文献
57.
Mori Toyoki Takeuchi Tadayoshi Ohura Makoto Miyakoda Goro Fujiki Hiroyuki Orito Kensuke Yoshida Kenji Hirano Takahiro Yamamura Yoshitaka Sumida Takumi Nakaya Yutaka Satake Hiromu Hata Fumiaki 《Molecular and cellular biochemistry》1998,178(1-2):335-343
Pranidipine, a new calcium channel modulator, prolonged endothelium-dependent relaxation induced by acetylcholine in a aortic ring preparation, contracted with prostaglandin F2. This action was not shared by amlodipine. The effect was not modified by indomethacin, suggesting that the action of pranidipine does not involve prostanoid metabolism. NG-nitro-L-arginine completely prevented the action of Pranidipine. The drug affected neither nitric oxide (NO) synthase activity nor the level of cyclic GMP in the vessel. Pranidipine did not affect the sensitivity of the contractile proteins to calcium. Pranidipine also did not alter cyclic GMP-induced relaxation in a-toxinskinned vascular preparations. Pranidipine also prolonged glyceryl trinitrate-induced relaxation in the endothelium denuded rat aorta. Furthermore, pranidipine enhanced relaxation of the aorta induced by glyceryl trinitrate even in the presence of methylene blue, a guanylyl cyclase inhibitor. This action was not modified by iberiotoxin or by charybdotoxin, two inhibitors of the calciumactivated potassium channel. The results strongly suggest that pranidipine enhances cyclic GMPindependent NO-induced relaxation of smooth muscle by a mechanism other than through NOinduced hyperpolarization. These effects were in direct contrast to amlodipine, another new 1,4dihydropyridine calcium antagonist. 相似文献
58.
Kurata H Kusumi K Otsuki K Suzuki R Kurono M Tokuda N Takada Y Shioya H Mizuno H Komiya T Ono T Hagiya H Minami M Nakade S Habashita H 《Bioorganic & medicinal chemistry letters》2012,22(1):144-148
Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice. 相似文献
59.
Baker DL Fujiwara Y Pigg KR Tsukahara R Kobayashi S Murofushi H Uchiyama A Murakami-Murofushi K Koh E Bandle RW Byun HS Bittman R Fan D Murph M Mills GB Tigyi G 《The Journal of biological chemistry》2006,281(32):22786-22793
Autotaxin (ATX, nucleotide pyrophosphate/phosphodiesterase-2) is an autocrine motility factor initially characterized from A2058 melanoma cell-conditioned medium. ATX is known to contribute to cancer cell survival, growth, and invasion. Recently ATX was shown to be responsible for the lysophospholipase D activity that generates lysophosphatidic acid (LPA). Production of LPA is sufficient to explain the effects of ATX on tumor cells. Cyclic phosphatidic acid (cPA) is a naturally occurring analog of LPA in which the sn-2 hydroxy group forms a 5-membered ring with the sn-3 phosphate. Cellular responses to cPA generally oppose those of LPA despite activation of apparently overlapping receptor populations, suggesting that cPA also activates cellular targets distinct from LPA receptors. cPA has previously been shown to inhibit tumor cell invasion in vitro and cancer cell metastasis in vivo. However, the mechanism governing this effect remains unresolved. Here we show that 3-carba analogs of cPA lack significant agonist activity at LPA receptors yet are potent inhibitors of ATX activity, LPA production, and A2058 melanoma cell invasion in vitro and B16F10 melanoma cell metastasis in vivo. 相似文献
60.
Atsushi Intoh Akira Kurisaki Dr. Yuko Yamanaka Hisashi Hirano Hiroyuki Fukuda Hiromu Sugino Makoto Asashima Professor 《Proteomics》2009,9(1):126-137
Embryonic stem cells (ESCs) are established from the inner cell mass of preimplantation embryos, are capable of self‐renewal, and exhibit pluripotency. Given these unique properties, ESCs are expected to have therapeutic potential in regenerative medicine and as a powerful tool for in vitro differentiation studies of stem cells. Various growth factors and extracellular matrix components regulate the pluripotency and differentiation of ESC progenies. Thus, the cell surface receptors that bind these regulatory factors are crucial for the precise regulation of stem cells. To identify membrane proteins that are involved in the regulation of pluripotent stem cells, the membrane proteins of murine ESCs cultured with or without leukemia inhibitory factor (LIF) were purified and analyzed by quantitative proteomics. 2‐D PAGE‐based analysis using fluorescently labeled proteins and shotgun‐based analysis with isotope‐labeled peptides identified 338 proteins, including transmembrane, membrane‐binding, and extracellular proteins, which were expressed specifically in pluripotent or differentiated murine ESCs. Functions of the identified proteins revealed cell adhesion molecules, channels, and receptors, which are expected to play important roles in the maintenance of murine ESC pluripotency. Membrane proteins that are expressed in pluripotent ESCs but not in differentiated cells such as Slc16a1 and Bsg could be useful for the selection of the stem cells in vitro. 相似文献