三种tyrphostin对大鼠肝酪蛋白激酶Ⅱ的作用(英文)

目的：研究ｔｙｒｐｈｏｓｔｉｎ对酪蛋白激酶Ⅱ（ＣＫⅡ）的作用．方法：依次采用ＤＥＡＥ纤维素和肝素Ｓｅｐｈａｒｏｓｅ层析将大鼠肝ＣＫⅡ进行了部分纯化，通过将去磷酸化的酪蛋白和［γ３２Ｐ］ＡＴＰ与ＣＫⅡ保温的方法测定ＣＫⅡ的活性．结果：ＡＧ３４对ＣＫⅡ有强烈的抑制作用ＩＣ５０３３μｍｏｌ·Ｌ－１（２７－４１μｍｏｌ·Ｌ－１），ＡＧ３７２（１２１μｍｏｌ·Ｌ－１）和ＡＧ１１１２（１５０μｍｏｌ·Ｌ－１）对ＣＫⅡ有明显的抑制作用．ＡＧ３４对ＣＫⅡ的动力学研究表明：它与酪蛋白和ＡＴＰ均呈非竞争性抑制作用．结论：ＡＧ３４、ＡＧ３７２和ＡＧ１１１２是ＣＫⅡ的抑制剂，ＡＧ３４的抑制作用与酪蛋白和ＡＴＰ均呈非竞争性．     

Tyrphositns对大鼠肝酪蛋白激酶Ⅱ活性的影响

目的；研究Ｔｙｒｐｈｏｓｔｉｎｓ（ＡＧ１２３，ＡＧ１３９４，ＡＧ１１４，ＡＧ１１０９，ＡＧ５５５）对酪蛋白激酶Ⅱ（ＣＫⅡ）活性的影响。方法：依次采用ＤＥＡＥ－纤维素和肝素Ｓｅｐｈａｒｏｓｅ层析将大鼠肝ＣＫⅡ纯化了１０４倍，通过将去磷酸化的酪蛋白和（γ－＾３２Ｐ）ＡＴＰ与ＣＸⅡ保温的方法测定ＣＫⅡ的活性。结果：ＡＧ２１３对ＣＸⅡ有强烈的抑制作用（ＩＣ５０４４．７μｍｏｌ．Ｌ＾－１（４１．５μｍｏｌ．     

Tyrphostins对大鼠肝酪蛋白激酶Ⅱ活性的影响(英文)

目的:研究Tyrphostins(AG123,AG1394,AG114,AG1109,AG555)对酪蛋白激酶Ⅱ(CKⅡ)活性的影响。方法:依次采用DEAE-纤维素和肝素-Sepharose层析将大鼠肝CKⅡ纯化了104倍,通过将去磷酸化的酪蛋白和[γ-~(32)P)ATP与CKⅡ保温的方法测定CKⅡ的活性。结果:AG213对CKⅡ有强烈的抑制作用(IC_(50)44.7μmol·L~(-1)[41.5μmol·L~(-1),47.9μmol·L~(-1)]),AG1394(144μmol·L~(-1))对CKⅡ的抑制率为89％。AG114和AG1109对CKⅡ也有明显的抑制作用,而AG555对CKⅡ的活性没有影响。结论:某些tyrphostins是CKⅡ抑制剂。     

5种抗血小板药对大鼠肝酪蛋白激酶Ⅱ的影响

用ＤＥＡＥ－纤维素和肝素－Ｓｅｐｈａｒｏｓｅ４Ｂ层析法部分纯化了大鼠肝酪蛋白激酶Ⅱ（ＣＫⅡ）；研究了５种抗血小板药对ＣＫⅡ活性的影响。结果表明，肝素对ＣＫⅡ有强烈的抑制作用，其ＩＣ５０为０．８８ｍｍ·Ｌ－１；蝙蝠葛碱、川芎嗪对ＣＫⅡ有明显的抑制作用（Ｐ＜０．０１），但较肝素的作用弱得多；汉防己碱对ＣＫⅡ活性没有明显影响；而潘生丁能使ＣＫⅡ活性明显升高，在一定范围内呈剂量依赖关系。这些结果可能对研究ＣＫⅡ是否在血小板的聚集和活化中起某些作用有重要的参考价值。     

依诺沙星对大鼠肝药酶的抑制作用

在肝微粒体水平上，采用依诺沙里４００ｍｇ／ｋｇ，灌胃ｑｄ×７ｄ能显著减少大鼠肝微粒体细胞色素Ｐ４５０。含量，经依诺沙星处理的大鼠肝微粒体中氨基比林－Ｎ－脱甲基酶、ＮＡＤＰＨ－细胞色素Ｃ还原酶、７－乙氧基香豆素－Ｏ－脱乙基酶、苯并芘羟化酶、戊巴比妥侧链羟化酶的活性均显著减弱。可见，依诺沙星对大鼠肝药酶具有广泛的抑制作用。     

激酶变构抑制剂: 一种新的高效和高选择性调节激酶活性的方式(英文)

研究证明, 激酶活性失控是导致癌症的原因之一, 癌细胞存活和增殖与相应激酶活性的失控密切相关。选择性的抑制激酶活性已经成为开发安全有效的抗癌药的重点研究领域。到目前为止, 已有15种激酶抑制剂得到美国食品药品监督管理局的批准用于治疗多种癌症。其中, 激酶的变构抑制剂在临床上显示出更好的安全性和有效性。本文将总结这些激酶的变构构象、它们对应的抑制剂及其作用方式。     

软肝宁对大鼠肝纤维化的保护作用研究

目的探讨软肝宁对肝纤维化大鼠的影响,为临床适应证提供实验依据。方法将60只大鼠随机分为6组。正常对照组给予生理盐水;模型组给予20%四氯化碳花生油溶液按10 mL/kg皮下注射,首剂加倍,每5 d注射1次,首次注射后,用生理盐水按10 mL/kg灌胃,1次/天,连续6周;秋水仙碱组配成0.01 g/L;软肝宁高、中、低剂量组（0.12,0.06,0.03 g/kg）按损伤模型组同法给予CCl4造模,然后给予软肝宁给药,1次/天。给药6周后检测大鼠血清中的丙氨酸氨基转移酶（ALT）、天门冬酸氨基转移酶（AST）、超氧化物歧化酶（SOD）、丙二醛（MDA）、血清透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原（PCⅢ）和羟辅氨酸（HYP）,并观察大鼠肝组织常规病理改变。结果软肝宁能改善肝纤维化大鼠的肝功能,高、中剂量可显著降低CCl4致大鼠肝损伤血清ALT,AST,MDA,HA,LN,PCⅢ水平和肝组织中过高的HYP（P〈0.05或P〈0.01）,并能升高血清中SOD含量。常规病理显示,中、高剂量软肝宁可明显减轻CCl4所致的大鼠肝细胞变性、坏死及肝组织损害程度。结论软肝宁具有延缓CCl4所致肝纤维化进程的作用。     

软肝宁的抗大鼠肝纤维化作用

目的探讨软肝宁对四氯化碳(CCl4)所致肝纤维化大鼠的影响。方法 60只雄性Wister大鼠均分为六组:除正常对照组外,其余五组采用CCl4复制肝纤维化大鼠模型后分为模型对照组、软肝宁高、中、低剂量组(软肝宁0.12,0.06,0.03g/kg)和秋水仙碱组。给药6周后检测大鼠血清ALT、AST、超氧化物歧化酶(SOD)、丙二醛(MDA)、总蛋白(TP)、白蛋白(ALB)及羟辅氨酸(Hyp),并行大鼠肝组织常规病理检查。结果模型对照组的ALT、AST、MDA和Hyp均高于正常对照组,而SOD、TP及ALB活性低于正常对照组(P<0.05或P<0.01)。软肝宁高、中剂量组的ALT、AST、MDA和Hyp均低于模型对照组,而SOD、TP及ALB活性均高于模型对照组(P<0.05或P<0.01)。病理检查显示,软肝宁中、高剂量组大鼠的肝组织损害明显比模型对照组轻。结论软肝宁具有延缓CCl4所致肝纤维化进程的作用。     

（一）-罗汉松脂素体外对酪蛋白激酶的强抑制作用

有报道称，从四川山矾Symplocos setchuensis中分得的(一)-罗汉松脂素(MTS)对H9淋巴细胞中的HIV复制有抑制作用，且MTS衍生物在体外对该病毒有更强的抑制作用。为研究MTS抗HIV机理，作者就该成分对2种酪蛋白激酶CK-I和CK-Ⅱ以及A-激酶和C-激酶活性的抑制作用进行了以下试验。     

Studies on 3-hydroxykynureninase from rat liver.

Kynureninase (L-kynurenine hydrolase E.C. 3.7.1.3.) was purified about 200 times from rat liver. The purified enzyme catalyzes the L-3-hydroxykynurenine leads to 3-hydroxyanthranilate reaction more favorably than the L-kynurenine leads to anthranilate reaction, with Km values of 1.67 x 10(-6) M for L-3-hydroxykynurenine and of 1.67 x 10(-4) M for L-kynurenine. Besides, this enzyme did not produce 5-hydroxyanthranilate from D,L-5-hydroxykynurenine. Therefore we think it is mainly a 3-hydroxykynureninase regulating the tryptophan degradation towards the formation of nicotinic acid necessary to NAD synthesis, rather than towards the accumulation of anthranilate.     

Synthesis and proapoptotic properties of new casein kinase II inhibitors

Casein kinase II (CK2) is the most pleiotropic of all protein kinases with more than 300 substrates implicated in a wide variety of cellular functions as signal transduction, proliferation and cell survival. Increased levels of CK2 has been demonstrated in a number of cancers, where it regulates the activity of various oncoproteins and tumor suppressor proteins. Therefore, CK2 inhibitors could be considered as potential anticancer drugs in monotherapy or in combination with known cytostatics. In this study, we examined proapoptotic activity of new strong CK2 inhibitor - 4,5,6,7-tetraiodobenzimidazole (TIBI) (IC50 = 38 nM) as well as new derivatives of 4,5,6,7-tetrabromobenzimidazole and 4,5,6,7-tetraiodobenzimidazole. All the tested compounds induced apoptosis and cytostatic effects in the promyelocytic leukemia cell line (HL-60). The proapoptotic effect was concentration and time dependent. The changes of the mitochondrial membrane potential and cell cycle progression were also observed.     

Action of khimcoccid on monoamine oxidase of rat liver mitochondria

Pharmaceutical Chemistry Journal -     

Action of quercetin on glycogen catabolism in the rat liver

1. The influence of quercetin on glycogen catabolism and related parameters was investigated in the isolated perfused rat liver and subcellular systems. 2. Quercetin stimulated glycogenolysis (glucose release). This effect was already evident at a concentration of 50 µ M maximal at 300 µ M and declined at higher concentrations. Quercetin also stimulated oxygen consumption, with a similar concentration dependence. 3. Lactate production from endogenous glycogen (glycolysis) was diminished by quercetin without significant changes in pyruvate production. 4. Quercetin did not inhibit glucose transport into cells but decreased intracellular sequestration of [5- 3 H]glucose under conditions of net glucose release. 5. In isolated mitochondria, quercetin diminished the energy transduction efficiency. It also inhibited several enzymatic activities, e.g. the K + -ATPase/Na + -ATPase of plasma membrane vesicles and the glucose 6-phosphatase of isolated microsomes. 6. No significant changes of the cellular contents of AMP, ADP and ATP were found. The cellular content of glucose 6-phosphate, however, was increased (3.12-fold). 7. Some of the effects of quercetin (glycogenolysis stimulation) can be attributed to its action on mitochondrial energy metabolism, as, for example, uncoupling of oxidative phosphorylation. However, the multiplicity of the effects on several enzymatic systems certainly produces an intricate interplay that also generates complex and apparently contradictory effects.