AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism

The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include the following: (1) the structural components of the three AMPK subunits (i.e. AMPKα, β, and γ), and their differential localization in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca²⁺/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-β-activated kinase 1 (TAK1); (3) the pharmacological agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle. Received 04 May 2008; received after revision 14 June 2008; accepted 14 July 2008     

Ikaros negatively regulates inducible nitric oxide synthase expression in macrophages: Involvement of Ikaros phosphorylation by casein kinase 2

Ikaros is known as a critical regulator of lymphocyte development. We examined the regulatory role of Ikaros in LPS/IFN-gamma-induced inducible nitric oxide synthase (iNOS) expression by macrophages. Our results showed that IK6 (Ikaros dominant negative isoform) induction increases the iNOS expression. Ikaros DNA binding activity on the iNOS promoter was decreased, and a mutation of the Ikaros-binding site on the iNOS promoter resulted in an increase in LPS/IFN-gamma-induced iNOS expression. LPS/IFN-gamma increased the histone (H3) acetylation on the Ikaros DNA binding site. These results suggest that Ikaros acts as a negative regulator on iNOS expression. Treatment with a casein kinase 2 (CK2) inhibitor reversed LPS/IFN-gamma-induced decrease in Ikaros DNA binding activity. Moreover, overexpression of kinase-inactive CK2 decreased iNOS expression and a significant amount of CK2alpha1 translocated into the nucleus in LPS/IFN-gamma-treated cells. Overall, these data indicate that LPS/IFN-gamma decreases the Ikaros DNA binding activity via the CK2 pathway, resulting in an increase of iNOS expression.     

Do cells think?

A microorganism has to adapt to changing environmental conditions in order to survive. Cells could follow one of two basic strategies to address such environmental fluctuations. On the one hand, cells could anticipate a fluctuating environment by spontaneously generating a phenotypically diverse population of cells, with each subpopulation exhibiting different capacities to flourish in the different conditions. Alternatively, cells could sense changes in the surrounding conditions – such as temperature, nutritional availability or the presence of other individuals – and modify their behavior to provide an appropriate response to that information. As we describe, examples of both strategies abound among different microorganisms. Moreover, successful application of either strategy requires a level of memory and information processing that has not been normally associated with single cells, suggesting that such organisms do in fact have the capacity to ‘think’. Received 3 January 2007; accepted 4 April 2007     

RACK1依赖的miRNA途径参与调节植物叶绿素的生物合成

为深入探索活化C激酶受体1(receptor of activated C kinase 1,RACK 1)在调节植物microRNA(miRNA)的生物发生,以及其靶基因中的关键作用,对在美国国家生物技术信息中心(National Center for Biotechnology Information,NCBI)网站上共享的基因表达综合数据库(Gene Expression Omnibus,GEO)中有关rack1突变体的小RNA序列数据重新进行了系统分析和挖掘,找到了19个新miRNA.通过解析差异miRNA表达,鉴定到了特异调控叶绿素合成相关基因HEMA和HEMC表达的miRNA,为今后深入系统地研究RACK1在调节叶绿体发育和光合作用机理提供了关键的理论依据,也为利用公共数据库挖掘潜在的数据信息提供了基本的研究设想和思路.     

基于分子对接研究吲哚咔唑类小分子对Tie-2/VEGFR2的双效抑制作用模式*

 运用分子对接技术研究了吲哚咔唑类小分子对人血管内皮生长因子受体2(VEGFR2)和人血管生成素受体Tie-2(ANG-R-Tie-2)的双效抑制作用模式。研究结果表明,吲哚咔唑类小分子的双效抑制作用主要源于两种受体相似的活性口袋,小分子与两者的铰链区均可形成氢键,使其催化活性受到抑制,从而抑制肿瘤细胞的生长。抑制活性的差异主要源于活性口袋的细微差异所导致疏水、静电等相互作用的不同。其中,疏水作用的差异是影响配体选择性的主要原因,静电作用、氢键及空间位阻对结合稳定也有一定影响。该文的研究结果为多靶点酪氨酸激酶小分子抑制剂的设计及提高激酶抑制剂的选择性提供了重要的理论依据。     

cAMP依赖蛋白激酶(PKA)磷酸化Nef蛋白对HIV复制的影响

目的:研究Nef PKA磷酸化位点对HIV复制的影响。方法:在全长HIVNL4-3中,通过将Nef Ser9突变为丙氨酸,构建一个单突变HIV DNA。接着用野生型HIV或单突变型HIV产生病毒,然后用病毒去感染外周血单核细胞(PBMC)。结果:与亲代病毒比较,单突变Ser9为丙氨酸的病毒下调了HIV在静息PBMC中的复制。结论 :该突变在消除静息原代细胞中Nef对HIV复制的影响起重要作用。研究结果显示,PKA对Nef磷酸化是静息细胞中病毒生命周期的重要步骤。     

穴位灸法对运动时机体血清CK、BLA及运动能力的影响

通过对运动员进行穴位施灸处理，并以西洋参作为对照，观察定量运动时血清CK（肌酸激酶）及BLA（血乳酸）含量的变化以及台阶指数的变化。经过2个月的施灸处理，结果表明艾灸可以明显降低运动时机体血清肌酸激酶（CK）的活性及血乳酸的含量，能明显提高肌体的台阶指数。本研究提示：灸法可以减轻运动性疲劳，提高机体的运动能力。     

复方中药调节男子皮艇运动员身体机能状态的研究

目的:探讨复方中药对男子皮艇运动员冬训大负荷训练后身体机能状态的调节效果.方法:选取处于冬训大负荷训练期间的河南男子皮艇运动员18名,随机分为实验组和对照组.实验组内服复方中药,对照组给予安慰剂,分别在服药前和服药后的第8d、第15d、第22 d、第29 d清晨取静脉血测定血红蛋白、肌酸激酶、尿素氮和睾酮,并于实验前后...     

PKB negatively modulates TGF-β responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3

Transforming growth factor-β (TGF-β) is a multi- functional growth regulator belonging to the TGF-β superfamily consisting of TGF-β, activin, bone mor- phological proteins and other factors. It regulates many aspects of cellular behavior, including mi…