The aging brain, a key target for the future: The protein kinase C involvement

The brain represents the primary centre for the regulation and control of all our body activities, receiving and interpreting sensory impulses and transmitting information to the periphery. Most importantly, it is also the seat of consciousness, thought, emotion and especially memory, being in fact able to encode, store and recall any information. Memory is really what makes possible so many of our complex cognitive functions, including communication and learning, and surely without memory, life would lose all of its glamour and purpose. Age-associated mental impairment can range in severity from forgetfulness at the border with pathology to dementia, such as in Alzheimer's disease. In recent years, one of the most relevant observations of research on brain aging relates to data indicating that age-related cognitive decline is not only due to neuronal loss, as previously thought; instead, scientists now believe that age-associated functional changes have more to do with the dysfunctions occurring over time. Within this context a prominent role is certainly played by signal transduction cascades which guarantee neuronal cell to elaborate coordinated responses to the multiple signals coming from the outside and to adapt itself to the environmental changes and requests. This review will focus the attention on protein kinase C pathway, with a particular interest on its activation process, and on the role of protein-lipid and protein-protein interactions to selectively localize the cellular responses. Furthermore, information is emerging and will be discussed on the possibility of mRNA stabilization through PKC activation. This review will also approach the issue on how alterations of these molecular cascades may have implications in physiological and pathological brain aging, such as Alzheimer's disease.     

瘦素受体在条件性厌味大鼠脑的表达

目的 :观察瘦素受体 (LR)在条件性厌味 (CTA)大鼠脑的表达 .方法 :采用高度特异的抗瘦素受体血清 ,用免疫组化ABC法观察LR在CTA和对照大鼠脑的分布与表达 .结果 :与对照组大鼠相比 ,CTA大鼠皮层Ⅲ层、视交叉上核、弓状核、杏仁基底外侧核、海马CA3、下丘脑外侧区等核团瘦素受体表达增加 (14 6vs 12 0 ,138vs 92 ,118vs 78,10 7vs70 ,85vs 38cells·mm-2 ,P <0 .0 5 ) ,而下丘脑前区、脑桥臂旁核、杏仁中央核瘦素受体表达减弱 (13vs2 6 ,70vs5 5 ,12 2vs 16 2cells·mm-2 ,P <0 .0 5 ) ,孤束核瘦素受体的表达与对照大鼠无显著性差异 (5 0vs 5 7cells·mm-2 ,P >0 .0 5 ) .结论 :瘦素可能通过杏仁核、臂旁核、海马、皮层的瘦素受体参与CTA的形成与维持     

p38丝裂原活化蛋白激酶信号级联在炎症反应中的作用

在急、慢性疾病中，细胞释放的炎症介质可以活化多种信号转导级联反应，丝裂原活化蛋白激酶(MAPK)信号转导通道在招募白细胞于炎症部位聚集起着重要的作用。同时，p38MAPK异构体的活化可以激活致炎细胞因子，而后刺激白细胞活化。然而，p38MAPK引起的白细胞招募这一系列的功能过程包括：粘附、游走和效应器的功能如氧化爆发以及p38MAPK介导的复杂细胞因子网络在炎症中的作用仍有待研究。针对减少炎症介质产生和以p38MAPK为治疗靶点的研究正在进行中，不远的将来可能会成为治疗炎症疾病的新策略。     

血管通透性的调节和游离微血管技术在其研究中的应用

Vascular hyperpermeability is a cardinal feature of inflammation or bum in which an array of inflammatory mediators can cause such changes in the microvessels. The fimctional measures of microvascular exchange that represent the properties of microvascular wails are the permeability coefficients which have been reported from measurements on intact whole organisms (including human subjects}, on perfused tissues and organs, on single perfused microvessels, and on monolayers of cultured microvascular endothelial cells. In this review, we summarize some experiments of vascular permeability in individually isolated perfused microvessels.     

An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

外源性三磷酸腺苷对肾小管上皮细胞增殖的影响

观察外源性三磷酸腺苷（ＡＴＰ）对肾小管上皮细胞株ＬＬＣＰＫ１增殖的影响。方法通过测定３Ｈ－胸腺嘧啶掺入、细胞计数以及细胞内丝裂素活化蛋白激酶活性，并与表皮生长因子（ＥＧＦ）的作用比较。结果发现ＡＴＰ呈浓度依赖性促进细胞的ＤＮＡ合成，并可使细胞计数增加，同时激活细胞内的丝裂素活化蛋白激酶，其作用与ＥＧＦ相似。腺苷与ＡＴＰ有类似作用，但较弱。核苷酸转运蛋白抑制剂对４－硝基苯６－硫基甙并不能抑制ＡＴＰ及腺苷的作用。结论细胞外ＡＴＰ可促进肾小管上皮细胞增殖，并可增强ＥＧＦ的促增殖作用，这一作用可能是通过膜受体介导的细胞内丝裂素活化蛋白激酶活化而实现的     

磷脂酶C与生殖

磷脂酶C(PLC)是磷脂酰肌醇信号转导途径中一个关键酶。目前确认的哺乳类PLC共有PLC β、PLC γ、PLC δ、PLC ε和最近新发现的PLC ζ 5种亚型 ,12种同工酶。不同亚型的结构、调控和组织分布各有差异。PLC在调控信号转导通路中的特性使其在顶体反应、卵子激活中发挥了巨大的作用。本文综述了PLC家族 5种亚型的结构、调控机制及PLC在男性生殖领域的相关内容 ,包括PLC引起卵子发生Ca2 + 振荡、激活卵子、促进胚胎发育等 ,并进一步探讨了PLC在临床上可能的应用前景。