Organic Solvents Activate Human Platelets Through the Inositol Lipid-linked Signal Transduction System

It has recently been proposed that occupational exposure to organic solvents in vivo may lead to platelet activation and this has been substantiated by exposure of platelets to solvents in vitro. The present work was undertaken to study the effects of organic solvents on the platelet inositol lipid signal transduction system. Human platelets that had been prelabelled with [³²P] P, were exposed to a saturated atmosphere of the organic solvents toluene, xylene or hexane. Extracts were analyzed for metabolites of the polyphosphoinositide cycle and ATP. All solvents studied induced a decrease in radioactivity in phosphatidylinositol 4,5-bisphosphate together with an increase in radioactivities in phosphatidylinositol 4-phosphate and phosphatidic acid. This is compatible with solvent-induced activation of the cells through the inositol lipid pathway. In cells exposed to toluene or xylene we could detect an increased level in inositol trisphosphates at 3 min of exposure. The solvent-induced changes in metabolic ATP could not explain the solvent-induced effects on the inositol lipid metabolism.

It is concluded that the organic solvents toluene, xylene and hexane can activate human platelets through the inositol lipid-linked transmembrane signal system.     

Leptin Signal Transduction in the HP75 Human Pituitary Cell Line

Leptin is an adipocyte-derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor (OB-R). Activation of the long form of OB-R (OB-Rb) results in JAK2 phosphorylation, activation of STATs, and subsequent gene expression. Activated STAT3 induces SOCS-3 expression in some cell types, which in turn down-regulates the JAK/STAT pathway. Although both leptin and OB-R are expressed in pituitary cells, the mechanism of signal transduction and its regulation in this organ has not been studied extensively. In these experiments we show that leptin reduces proliferation in a human pituitary cell line (HP75) and also increased apoptosis in these cells. Leptin also increased SOCS-3 mRNA and protein expression and tyrosine-phosphorylation in the HP75 human pituitary cell line. These findings suggest that SOCS-3 plays an important role in the inhibition of proximal leptin signal transduction in the anterior pituitary.     

Signal Transduction of Chemokine Platelet Factor 4 in Human Erythroleukemia Cells

Previous data have demonstrated that CXC-chemokine platelet factor 4 (PF4) inhibits the proliferation of the human erythroleukemia cell line (HEL). However, the mechanism of action is unclear at present. The signaling transduction induced by PF4 in the HEL was compared with that induced by transforming growth factor beta1 (TGF-beta1), which is also a potent inhibitor of HEL growth. It was found that PF4 had no inhibitory effect on intracellular calcium levels in resting HEL cells. When HEL cells were stimulated with interleukin-3 (IL-3), a rapid increase in the intracellular level of free calcium occurred within 15 to 20 seconds, and this increase was followed by a sustained increase that gradually declined until resting levels were reached 30 to 40 minutes later. PF4 dramatically decreased the transient rise of [Ca2+] and protein kinase C (PKC) activity of HEL cells induced by IL-3. However, PF4 had no inhibitory effect on PKC activation in resting HEL cells. Furthermore, PF4 was found to down-regulate significantly protein tyrosine kinase (PTK) activity. In contrast, TGF-beta1 induced an increase in intracellular free calcium concentration and PKC and PTK activity in HEL cells. Furthermore, PF4 significantly increased the messenger RNA (mRNA) level of p21waf1 in HEL cells. These data demonstrate that PF4 acts on HEL cells through a signaling transduction pathway, which is different from that of TGF-beta1 and is related to the up-regulatory mRNA level of p21waf1 in HEL cells.     

促红细胞生成素:新的心血管系统信号转导分子

传统认为促红细胞生成素(EPO)仅作用于造血细胞,最新研究表明它具有一些非造血效应,如在心肌缺血/再灌注时,有抗凋亡、抗炎等作用,认为它是心血管系统一个新的信号转导分子.其心血管保护作用无疑拓展了心血管疾病研究和治疗的新思路.临床上,EPO用于治疗心力衰竭或肾衰性贫血,不仅纠正贫血,而且改善心功能,提高患者的生活质量.但尚需进一步研究EPO心肌保护的分子机制,以阐明其在心血管系统中的治疗作用.     

ERK／MAPK信号转导通路与消化系肿瘤

细胞外信号调节激酶（ERK）/丝裂原活化蛋白激酶（MAPK）通路是经典的细胞信号转导途径,具有调节细胞增殖、分化、凋亡等多重功能,与肿瘤的发生、发展、转移、预后等密切相关,在临床诊治中具有重要的参考意义.本文重点探讨ERK/MAPK信号通路与消化系肿瘤发病、演进的关系及其潜在的分子机制,并对近期相关的临床应用作一详细介绍.     

The Growth Modulation and Postreceptor Signal Transduction of PACAP on Human Pancreas Carcinoma Cell Strains

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to posses mitogenic activity in some carcinomatic cells and normal cells. The present study was designed to investigate the growth modulation of PACAP on three kinds of human pancreas carcinoma cell strains (JF305, HS766T and ASPC-l) and its pathways of postreceptor signal transduction, role of sphingomyelin as a second messenger.     

疏血通改善低氧肺动脉高压作用与NO通路相关性

目的观察疏血通降低低氧肺动脉高压患者肺动脉压力作用与NO通路间的相关性。方法将34例确诊低氧肺动脉高压患者随机分为对照组及疏血通组,分别给予常规治疗和常规加疏血通治疗,分别测量治疗前及用药2周后两组患者mPAP、RVAW及RVAW/LVPW变化情况,采用Western Blot法测定治疗前、后两组患者组织中NOs、NO含量的变化,采用SPSS13.0软件分析数据。结果疏血通组及对照组治疗后mPAP、RVAW均明显降低(P<0.05),RVAW/LVPW比值下降(P<0.05),疏血通组及对照组治疗后组织中NOs、NO含量均明显增高(P<0.05),疏血通组mPAP、RVAW、RVAW/LVPW比值下降较对照组下降更为明显(P<0.05),疏血通组较对照组治疗后组织中NOs、NO含量增高更明显(P<0.05)。结论疏血通可降低低氧肺动脉高压患者肺动脉压力,其降低肺动脉压力作用可能与激活NOs提高组织中NO含量相关。     

氨基胍对非酶糖基化人脐静脉内皮细胞信号转导物DAG影响

目的： 为探讨氨基胍（ＡＧ）对非酶糖化（ＮＧＥｓ）引起的人脐静脉内皮细胞信号（ＤＡＧ）转导的影响及其机制。方法：采用薄层层析、放射自显影及放射酶标法分离、检测细胞中ＤＡＧ含量,应用荧光法检测ＮＧＥｓ的含量。结果：氨基胍组荧光值从２７．８±５．９（ＡＦＵ）降为８．５±２．８（ＡＦＵ） ,ＤＡＧ含量从５４１．５±４６．２３ ｐｍ ｏｌ·Ｌ－ １ 降为２５３．５±１８．２０ ｐｍ ｏｌ·Ｌ－ １。结论：氨基胍明显阻断糖基化终末产物（ＮＧＥｓ）的形成,并且由ＮＧＥｓ刺激内皮细胞产生的ＤＡＧ含量显著降低。这对糖尿病的慢性并发症防止提供了重要的理论依据     

Human Kidney Cathepsins B and H Activate and Lower the Molecular Weight of Human Inactive Renin

Cathepsins B, H, and D, extracted from human kidneys, activate human inactive renin. Inactive renin, obtained from human kidneys, contains two components of Mr 53,000 and 50,000. Upon incubation with 0.5 μM cathepsin B, the Mr of the larger component decreased progressively to 45,000 (similar to the Mr of active renin) without appreciable loss of renin activity. Cathepsin H also activated and decreased the Mr of kidney inactive renin. Plasma inactive renin was activated by the thiol proteases, cathepsins B and H, with less reduction in Mr than that observed in kidney renin.     

Investigating the Signal Transduction Pathways Underlying Remote Ischemic Conditioning in the Porcine Heart

Background  

The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion.     

姜黄素抗脑缺血再灌注损伤作用与MAPK信号通路的相关性分析

目的 探讨姜黄素对大鼠脑缺血再灌注损伤中细胞外信号调节蛋白激酶(ERK1/2)、C-Jun氨基末端(JNK)/应激化蛋白激酶(SAPK)及p38MAPK信号转导通路的影响.方法 采用线栓法阻塞大鼠大脑中动脉(MCAO)建立局灶性脑缺血模型,观察不同浓度姜黄素(20 mg/kg、40 mg/kg、80 mg/kg)对脑缺血再灌注损伤后大鼠神经行为学评分的影响,并用Western blot法检测p38MAPK、P-p38MAPK、ERK1/2、P-ERK1/2及JNK的表达.结果 假手术组无神经行为学改变;各用药组神经行为学评分明显低于缺血再灌注组(P<0.05).与缺血再灌注组相比各用药组p-p38MAPK及JNK表达明显降低(P<0.05),而P-ERK1/2表达显著增加(P(0.05),p38MAPK及ERK1/2表达各组间差异无统计学意义(P>0.05).结论 姜黄素对大鼠脑缺血再灌注损伤具有保护作用,其保护作用机制可能与抑制p38MAPK和JNK/SAPK信号转导通路以及增强ERK1/2信号转导通路有关.     

Mepacrine Stains the Dense Bodies of Human Platelets and not Platelet Lysosomes

S ummary . Mepacrine, used as a vital stain, accumulates in the lysosomes of most cells. In platelets, however, it does not stain the lysosomes but is a specific marker for dense bodies.