Non-host-selective fungal phytotoxins: Biochemical aspects of their mode of action

During the last decade increasing attention has been directed towards the biochemical mechanisms responsible for the biological activity of phytotoxins. Studies on the mode of action of some non-host-selective phytotoxins, some following on from previous observations, have demonstrated a very specific interaction with particular components of the cell machinery, and have suggested the possible use of these phytotoxins as tools for the investigation of important biochemical processes. This review article reports and discusses results of studies carried out in the 1980s with seven non-host-selective fungal toxins: brefeldin A, cercosporin,Cercospora beticola toxin, fusicoccin, ophiobolins, tentoxin, and zinniol. Each of these interferes with the life of the host by interacting with a different biochemical target.     

Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine onTrypanosoma cruzi

Summary The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes ofTrypanosoma cruzi, at concentrations lower than 100 M, and motility and infectivity of the bloodstream trypomastigote form at 200 M. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 M TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.     

2,6—二硝基甲苯对鲤鱼的毒性

研究测定了２,６－二硝基甲苯（２,６－ＤＮＴ）对鲤鱼的急性和亚致死毒性．亚致死试验经１８０ｍｇ／Ｌ、３６０ｍｇ／Ｌ、５４０ｍｇ／Ｌ、７２０ｍｇ／Ｌ、９９０ｍｇ／Ｌ２,６－ＤＮＴ暴露２１ｄ．在１５℃～１９℃下,２４ｈ、４８ｈ、７２ｈ、９６ｈ的半致死浓度值分别为２５４８ｍｇ／Ｌ、２２９６ｍｇ／Ｌ、２０１２ｍｇ／Ｌ、１９００ｍｇ／Ｌ．亚致死试验中,根据２,６－ＤＮＴ对鲤鱼生长和肝、肾、鳃ＡＴＰａｓｅ活力的影响,求得２,６－ＤＮＴ的最大允许毒物浓度为１８０～３６０ｍｇ／Ｌ．     

石刁柏非胚性细胞和胚性细胞的超微结构及ATP酶的定位

对石刁柏非胚性细胞及胚性细胞的超微结构及ＡＴＰ酶定位进行了观察，非胚性细胞内液泡大，大量的自体吞噬泡出现，在液泡膜上有ＡＴＰ酶的活性反应．胚性细胞的细胞核大，核移中，线粒体，质体，核糖体，高尔基体，内质网等细胞器增多，淀粉、脂滴积累，有较活跃的自体吞噬现象．细胞壁开始增厚，在细胞核，液泡膜，线粒体，内质网等部位有较高的ＡＴＰ酶活性，在部分细胞壁中也存在有ＡＴＰ酶活性反应沉淀     

人源fidgetin like-1蛋白AAA结构域的重组表达及酶学性质分析

Fidgetin是2000年发现的一个AAA蛋白家族新成员,同源序列分析表明它与ka-tanin、spastin属于AAA家族的同一亚家族,因此可能也具有ATP依赖的微管切割活性,ATP的结合和水解应该发生于fidgetin蛋白中保守的AAA结构域.在大肠杆菌中重组表达的人源fidgetin like-1(FIGL-1)蛋白的AAA结构域片段(HsFIGL-1-AAA),纯化后的最终产率为每升5 mg蛋白.与AAA蛋白通常形成六聚体不同,HsFIGL-1-AAA在溶液中为单体,且其ATPase活性很低,仅为0.0063 s-1.与其他AAA蛋白的序列比对发现,Sensor 2 motif中保守的Arg残基在HsFIGL-1-AAA结构域中为Thr,但该位点的突变T609R并未明显改变该蛋白的ATPase活性.这些结果提示HsFIGL-1可能以一种特殊的方式发挥功能,这为进一步研究fidgetin及其同源蛋白的结构和功能奠定了基础.     

Molecular mechanisms in therapy of acid-related diseases

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007     

不同负荷游泳训练对大鼠红细胞膜的影响

目的探讨不同负荷游泳训练对大鼠的运动能力、抗氧化酶SOD的活性、脂质过氧化产物MDA含量、Na -K -ATP酶和Ca2 -ATP活性的影响。方法选取雄性SD大鼠60只,随机分为三大组,即对照组(C组,20只)、小负荷游泳训练组(L组,20只)、大负荷游泳训练组(H组,20只),测试不同负荷游泳训练对大鼠红细胞膜抗氧化能力和ATP酶活性的影响。结果小负荷的运动训练可以降低安静时红细胞膜上MDA含量,提高抗氧化酶SOD活性,大负荷的训练则产生相反的结果;力竭运动后小负荷训练组红细胞膜Na -K -ATP酶活性增加,大负荷训练组Na -K -ATP酶活性下降;力竭运动后即刻各组RBCM上Ca2 -ATP酶活性都有下降,安静时小负荷的运动训练组Ca2 -ATP酶活性提高,但没有显著性差异,大负荷的运动训练使Ca2 -ATP酶活性显著下降。结论小负荷的运动训练可以提高机体的运动能力,而大负荷的训练会对机体产生不良影响;适宜负荷的运动训练不但可以提高安静时酶的活性,而且可以提高酶活性的储备力,延缓运动性疲劳的发生及抵抗力竭运动对机体造成运动损伤。     

Mechanical and biochemical characterization of the contraction elicited by a calcium-independent myosin light chain kinase in chemically skinned smooth muscle

Summary The contraction induced by a Ca²⁺-independent myosin light chain kinase (MLCK-) was characterized in terms of isometric force (F_o), immediate elastic recoil (SE), unloaded shortening velocity (V_us), shortening under a constant load and ATPase activity of chemically skinned smooth muscle preparations. These parameters were compared to those measured in a Ca²⁺-induced contraction to assess the nature of cross bridge interaction in the MLCK-induced contraction. F_o developed in chicken gizzard fibers as well as SE were similar in contractions elicited by either agent. V_us in the contraction induced by MLCK-(0.36 mg/ml) was similar though averaged 39.3±8.9% less than V_us induced by Ca²⁺ (1.6x10^–6M) in the control fibers. Addition of Ca²⁺ (1.6x10^–6M) to a contraction induced by MLCK-resulted in small increases in both F_o and V_us. Shortening under a constant load was similar for both types of contractions. The contraction induced by MLCK-was accompanied by an increased rate of ATP hydrolysis. The MLCK-induced contraction is thus kinetically similar though not identical to a contraction induced by Ca²⁺. We conclude that with respect to actin-myosin interaction, MLCK- and Ca²⁺-induced contractions are similar.     

The plasma membrane calcium pump: Recent developments and future perspectives

The Ca²⁺ pump of the plasma membrane (PMCA) is regulated by a number of agents. The most important is calmodulin (CaM), which binds to a domain located in the C-terminal portion of the pump, removing it from an autoinhibitory site next to the active site. The CaM-binding domain is preceded by an acidic sequence which contains a hidden signal for endoplasmic reticulum (ER) retention. Chimeras of the PMCA and endoplasmic reticulum (SERCA) pumps have revealed the presence of a strong signal for ER retention in the first 45 residues of the SERCA pump. Four gene products of the PMCA pump are known: two of them (1 and 4) are ubiquitously expressed, two (2 and 3) are specific for nerve cells and may be induced by their activation. Mutagenesis work has identified four residues in three of the transmembrane domains of the pump which may be components of the trans-protein Ca²⁺ path. The mutation of two of these residues alters the membrane targeting of the pump.