蛋白激酶与细胞凋亡信号及凋亡抑制信号的转导

蛋白激酶主要有蛋白激酶A(PKA) ,蛋白激酶C(PKC) ,钙调蛋白依赖性蛋白激酶(CaM激酶 ) ,酪氨酸蛋白激酶 (TPK)等。近年来的研究表明 ,蛋白激酶参与了多种多样细胞凋亡的信号转导 ,并戏剧性地调节着细胞凋亡 ,有时加速凋亡 ,有时却可延迟凋亡。本文就蛋白激酶在细胞凋亡及凋亡抑制信号转导中的作用 ,以及转导凋亡信号和转导凋亡抑制信号的两类不同途径与Caspase家族的关系加以综述     

局灶性脑缺血再灌注信号转导与转录激活子1的表达与磷酸化

目的：观察局灶性脑缺血再灌注信号转导与转录激活子1蛋白表达及其丝氨酸残基磷酸化，探讨其在神经元凋亡中的作用。 方法：实验于2003-04／2004-01在中南大学湘雅医院神经病学研究所和中心实验室完成。选择雄性SD大鼠52只，随机分为空白对照组4只。假手术组16只，脑缺血组32只，脑缺血组又分为再灌注15min，1，4，12，24，48h，5，7d8个时相点，每个时相点4只。采用线栓法制作短暂性局限脑缺血模型。造模后进行神经功能评分，0分：正常，未见任何神经功能缺损表现。1分：垂直提起时前爪不能伸直。2分：行走时身体向左倾，向左侧旋转。3分：行走时身体向左侧跌倒。4分：不能自发行走或有意识障碍。根据首次评分，没有神经功能缺损、评分4分、有呼吸困难、提前死亡及处死时发现有蛛网膜下腔出血的动物均弃去。此外对于手术中出血过多的动物也弃去。采用免疫组织化学技术依靠特异性抗体检测信号转导与转录激活子1蛋白表达及其丝氨酸残基磷酸化。 结果：纳入动物52只，均进入结果分析。①信号转导与转录激活子1于再灌注1h检测到阳性表达，12h达到峰值，24h下降[分别为（16．90&;#177;2．95），（28．40&;#177;4．62），（18.68&;#177;2．72）个]。②信号转导与转录激活子1磷酸化于再灌注15min出现，4h达到峰值，持续至少5d[分别为（7.87&;#177;1．82），（28.43&;#177;5．94），（10．25&;#177;2．48）个]。 结论：脑缺血再灌注信号转导与转录激活子1表达上调并在丝氨酸残基磷酸化，可能参与再灌注神经元凋亡。     

局灶性脑缺血再灌注信号转导与转录激活子1的表达与磷酸化

目的:观察局灶性脑缺血再灌注信号转导与转录激活子1蛋白表达及其丝氨酸残基磷酸化,探讨其在神经元凋亡中的作用。方法:实验于2003-04/2004-01在中南大学湘雅医院神经病学研究所和中心实验室完成。选择雄性SD大鼠52只,随机分为空白对照组4只,假手术组16只,脑缺血组32只,脑缺血组又分为再灌注15min,1,4,12,24,48h,5,7d8个时相点,每个时相点4只。采用线栓法制作短暂性局限脑缺血模型。造模后进行神经功能评分,0分:正常,未见任何神经功能缺损表现。1分:垂直提起时前爪不能伸直。2分:行走时身体向左倾,向左侧旋转。3分:行走时身体向左侧跌倒。4分:不能自发行走或有意识障碍。根据首次评分,没有神经功能缺损、评分4分、有呼吸困难、提前死亡及处死时发现有蛛网膜下腔出血的动物均弃去。此外对于手术中出血过多的动物也弃去。采用免疫组织化学技术依靠特异性抗体检测信号转导与转录激活子1蛋白表达及其丝氨酸残基磷酸化。结果:纳入动物52只,均进入结果分析。①信号转导与转录激活子1于再灌注1h检测到阳性表达,12h达到峰值,24h下降[分别为(16.90±2.95),(28.40±4.62),(18.68±2.72)个]。②信号转导与转录激活子1磷酸化于再灌注15min出现,4h达到峰值,持续至少5d[分别为(7.87±1.82),(28.43±5.94),(10.25±2.48)个]。结论:脑缺血再灌注信号转导与转录激活子1表达上调并在丝氨酸残基磷酸化,可能参与再灌注神经元凋亡。     

细胞骨架与力学信号传导

背景：细胞在感受力学刺激后,通过一定的信号转导机制,将力学信号转换成化学信号,进而实现其生物功能。在这一系列的信号转导过程中,横贯细胞的细胞骨架作为枢纽,发挥着重要作用。 目的：通过系统的分析和总结细胞骨架在力学信号转导通路中的作用机制,为细胞骨架相关疾病的临床治疗提供潜在的治疗靶点。 方法：以英文检索词为“cytoskeleton,microtubules,microfilaments,intermediate filaments,mechanical stimulation,signal transduction ”及中文检索词为“细胞骨架、微管、微丝、中间纤维丝、机械刺激、信号传导”,由第一作者检索1990至2012年PubMed 数据库及中国知网中文科技数据库,查阅近年机械刺激对细胞骨架影响的相关文献,最终保留48篇文献。 结果与结论：机械刺激是细胞增殖、生长发育以及凋亡的重要因素。随着对细胞骨架认识的逐渐深入,人们发现细胞骨架在细胞对力学刺激的感受和信息传导的过程中起重要作用。机械刺激作用于细胞后,通过 Rho家族蛋白、蛋白激酶C、整合素以及丝裂原激活蛋白激酶等多条信号通路,且各种信号传导通路中存在交联,从而影响细胞骨架的重组,并将力学刺激进一步转换成化学信号,最终完成其生物效应。     

Ras信号转导通路

Ras在信号转导、细胞增殖、恶性转化、肿瘤侵袭转移等方面起重要作用。本文着重介绍了ras癌基因、Ras蛋白的生化特性以及Ras信号转导通路中信号分子的具体作用和潜在的治疗作用靶点     

PPARs-mediated intracellular signal transduction

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are activated by fatty acids and their derivatives. PPARs consist of three isotypes named PPARalpha (NR1C1), PPARbeta/delta (NR1C2) and PPARgamma (NR1C3) in vertebrates. Each of them is encoded in a separate gene and binds fatty acids and eicosanoids. Although each isotype fulfills distinct functions, PPARs function not only as an important fatty acid sensor that regulate lipid, carbohydrate and amino acid metabolism but also play an important role in various signaling pathways (immunity, inflammation, apoptosis and cell differentiation). In this review, I focus on emerging knowledge about PPARs roles in various intracellular signaling pathways.     

Eicosanoids, mesangial contraction, and intracellular signal transduction.

The glomerular mesangial cell is a specialized pericyte with multiple functional capabilities including contraction. Mesangial contraction may reduce the glomerular filtration surface area and hence the ultrafiltration coefficient, Kf. Cultured mesangial cells convert arachidonic acid into biologically active eicosanoids which are either contractile (thromboxane A2 [TxA2], prostaglandin F2 alpha [PGE2 alpha]) or relaxant (PGE2, PGI2). The addition of TxA2 analogues, PGE2 or sulfidopeptide leukotrienes (LTC4 and LTD4) stimulated contraction of cultured mesangial cells with threshold responses at approximately 1 nM and maximum responses at 1 microM. PGE2 and PGI2 antagonized mesangial contraction induced by TxA2 analogues. Contraction was enhanced by inhibiting mesangial cyclooxygenase with nonsteroidal antiinflammatory drugs (NSAID). Contractile eicosanoids stimulated phospholipase C thereby elevating intracellular inositol trisphosphate and cytosolic free Ca2+ concentration ([Ca2+]i). Vasorelaxant prostanoids stimulated adenylate cyclase, increasing intracellular cyclic AMP. We conclude that eicosanoids control mesangial contractility by regulating [Ca2+]i and cAMP. NSAID increase mesangial reactivity by blocking the inhibitory effects of endogenous vasodilator eicosanoids, with potential consequences on glomerular hemodynamics.     

Transforming growth factor-beta signal transduction in epithelial cells.

Transforming growth factor (TGF)-beta is a natural and potent growth inhibitor of a variety of cell types, including epithelial, endothelial, and hematopoietic cells. The ability of TGF-beta to potently inhibit the growth of many solid tumors of epithelial origin, including breast and colon carcinomas, is of particular interest. However, many solid tumor cells become refractory to the growth inhibitory effects of TGF-beta due to defects in TGF-beta signaling pathways. In addition, TGF-beta may stimulate the invasiveness of tumor cells via the paracrine effects of TGF-beta. Accordingly, in order to develop more effective anticancer therapeutics, it is necessary to determine the TGF-beta signal transduction pathways underlying the growth inhibitory effects and other cellular effects of TGF-beta in normal epithelial cells. Thus far, two primary signaling cascades downstream of the TGF-beta receptors have been elucidated, the Sma and mothers against decapentaplegic homologues and the Ras/mitogen-activated protein kinase pathways. The major objective of this review is to summarize TGF-beta signaling in epithelial cells, focusing on recent advances involving the Sma and mothers against decapentaplegic homologues and Ras/mitogen-activated protein kinase pathways. This review is particularly timely in that it provides a comprehensive summary of both signal transduction mechanisms and the cell cycle effects of TGF-beta.     

Thyrotropin receptor--structure, autoantibody and signal transduction

Thyrotropin receptor (TSHR) belongs to type A G protein-coupled receptor family, which possesses a large entracellular domain (ED). Recent studies have revealed the importance of leucine rich repeats domain in the ED and the formation of oligomer in its TSH binding and its signal transduction. TSHR binds to Gs and Gq. It might also activate JAK/STAT kinase system. To further understanding the pathophysiology of Graves' disease, it will be needed to clarify the epitopes of thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody(TSBAb) and thyroid growth-stimulating IgG (TGI) and their relation to signal transduction pathway.