氨基酸转运体在肿瘤代谢中的研究进展

代谢重编程是肿瘤的重要特征,是指肿瘤细胞为满足其快速增殖的生物合成与能量需求,对其糖代谢、脂代谢以及氨基酸代谢等代谢路径进行的重编程,以维持增长速度以及补偿能量代谢所造成的氧化还原压力。虽然不同的癌症代谢变化不同,但有些特征是所有癌症共有的,氨基酸代谢重编程是其中一个重要的特征。氨基酸进出细胞需要氨基酸转运体的协助,因而在肿瘤细胞中多种特定的氨基酸转运体均过表达。靶向氨基酸转运体通过影响肿瘤细胞的氨基酸代谢从而达到抗肿瘤的目的,是目前抗肿瘤药物的研究热点之一。主要介绍了几种在肿瘤代谢中发挥重要作用的氨基酸转运体以及靶向氨基酸转运体抗肿瘤治疗的研究进展及相关作用机制,旨在了解氨基酸转运体在抗肿瘤研究中的作用,以期促进靶向氨基酸转运体抗肿瘤药物的发展。     

植物中抗坏血酸的生物学功能研究进展

抗坏血酸是水溶性抗氧化有机小分子,在植物中广泛存在,并可作为某些氧化还原酶的辅酶。本文主要综述了抗坏血酸在植物中的合成、转运和所参与的多种生理作用,如细胞周期调控、成花诱导、光合结构保护、碳代谢和胁迫响应等,并对今后植物中抗坏血酸的相关研究提出展望。     

植物谷胱甘肽代谢与环境胁迫

谷胱甘肽是植物体内普遍存在的小分子抗氧化物质,它在还原态硫的储存和转运、蛋白质和核酸的合成、酶活性的调节、组织抗氧化特性的维持以及对氧化还原敏感的信号传导的调节中起着重要作用。谷胱甘肽库的大小及其氧化还原状态也与植物对多种生物异源物质及生物与非生物环境胁迫的忍耐密切相关。本文简要综述了近年来人们在植物谷胱甘肽生物合成与代谢、转运、信号传导以及胁迫响应中所取得的研究进展。     

SLC25A51——首次发现的哺乳动物细胞线粒体NAD+转运体

烟酰胺腺嘌呤二核苷酸(NAD⁺)及其还原形式NADH是糖酵解和线粒体呼吸作用中重要的辅因子,在能量代谢中发挥重要作用。当线粒体缺乏NAD⁺细胞因不能持续产生ATP而出现功能异常。以往研究发现酵母与植物的线粒体上均存在NAD+转运体,可以将NAD+转运至线粒体。但哺乳动物线粒体内膜上是否有NAD+转运体,一直存有争议。近来,美国宾夕法尼亚一研究团队首次证明SLC25A51可以在哺乳动物线粒体上发挥NAD+转运蛋白的功能。     

微生物有机酸转运蛋白的研究进展

转运蛋白是一类膜蛋白,可介导生物膜内外化学物质的跨膜转运及信号交换。有机酸转运蛋白在微生物有机酸代谢的跨膜转运过程中发挥重要作用,根据转运蛋白有机酸转运的方向不同可以分为摄取转运蛋白和外排转运蛋白。在微生物代谢中,有些有机酸可以作为能源直接参与体内代谢,有些是能量转换过程中的重要中间产物;摄取转运蛋白的过表达,可以促进微生物细胞获取能源物质,高效的生产目标产物;有机酸摄取转运蛋白敲除或外排转运蛋白表达,有利于底盘细胞外排更多目标产物,进而促进有机酸的生物合成。研究有机酸转运蛋白的结构和功能,有助于解析微生物细胞有机酸生物合成及利用的机制,对于提高工业微生物对有机酸的利用及生物合成具有重要作用。本文综述了微生物有机酸转运蛋白分类和结构、转运方式和转运功能等方面,重点综述了转运蛋白在有机酸生产中的应用,为工业微生物有机酸的高效生物合成及未来发展提供参考。     

植物抗坏血酸过氧化物酶的表达调控以及对非生物胁迫的耐受作用

抗坏血酸过氧化物酶(Ascorbate peroxidase, APX)属于I型血红素过氧化物酶, 它催化H2O2依赖的L-抗坏血酸氧化作用, 对抗坏血酸表现出高度的专一性。植物APX基因家族由4个亚家族组成, 分别为细胞质、叶绿体、线粒体和过氧化物酶体基因亚家族, 每个亚家族中又含有不同的APX同工酶。作为植物抗坏血酸-谷胱甘肽循环中的一个关键组分, APX在细胞H₂O₂代谢过程中起着至关重要的作用。研究表明植物APX是氧化还原信号系统中调节细胞水平H₂O₂非常重要的一种酶, APX同工酶的表达机制非常复杂, 细胞质APX受多种信号调节表达, 两种叶绿体APX通过选择性剪接进行组织特异性调节。通过调控产生的APX可调节细胞中的氧化还原信号, 进而提高植物对非生物胁迫的耐受性。文章综述了植物APX的催化机制、表达调控机理以及响应植物非生物逆境胁迫的重要作用。     

高等植物尿素代谢及转运的分子机理

尿素广泛存在于自然界中, 是易于被许多生物(如植物)利用的生长氮源。该文通过概述尿素在不同生命系统中存在的基础生理意义及各类型尿素转运蛋白, 讨论了植物细胞中尿素合成与分解的各种途径及尿素在植物氮营养、代谢和运输中的生理作用。迄今为止, 在植物中已发现了2类转运尿素的膜蛋白, 即MIPs和DUR3, 它们分别在低亲和力、高亲和力尿素运输中发挥潜在作用。异源表达结果表明, MIPs介导了尿素的被动迁移; 而AtDUR3则参与拟南芥根系对尿素的吸收。对MIPs和DUR3转运尿素的酶学特征、亚细胞作用位点和表达调控状况等的研究表明: 它们的分子生物学功能与植物的氮营养及氮素再分配和利用相关。     

高等植物尿素代谢及转运的分子机理

尿素广泛存在于自然界中,是易于被许多生物（如植物）利用的生长氮源。该文通过概述尿素在不同生命系统中存在的基础生理意义及各类型尿素转运蛋白,讨论了植物细胞中尿素合成与分解的各种途径及尿素在植物氮营养、代谢和运输中的生理作用。迄今为止,在植物中已发现了2类转运尿素的膜蛋白,即MIPs和DUR3,它们分别在低亲和力、高亲和力尿素运输中发挥潜在作用。异源表达结果表明MIPs介导了尿素的被动迁移：而AtDUR3则参与拟南芥根系对尿素的吸收。对MIPs和DUR3转运尿素的酶学特征、亚细胞作用位点和表达调控状况等的研究表明：它们的分子生物学功能与植物的氮营养及氮素再分配和利用相关。     

药物代谢酶及转运体与前列腺癌药物治疗

药物代谢酶是催化体内摄入的各种药物进行生物转化的一系列重要酶,属于生物转化酶系中的一类.虽然药物生物转化的主要场所在肝脏,但在肝外组织(如前列腺)亦存在,而且可影响药物在局部的生物转化率.药物转运体在药物的跨膜转运中发挥了重要的作用,影响了药物在体内的药代动力学进程,药物转运体在组织中分布广泛;本文着重阐述这些药物代谢酶及转运体在治疗前列腺癌药物中的作用,及它们在前列腺中的特异性表达,同时讨论了在不同的治疗策略中与药物代谢酶及转运体相关的靶向作用.     

高等植物钾转运蛋白

钾在植物生长发育过程中具有许多重要的作用。以模式植物拟南芥中克隆和鉴定的钾通道和转运体为基础,全面介绍了高等植物中钾转运体系家族,包括Shaker通道、KCO通道、KUP/HAK/KT转运体、HKT转运体和其它转运体。同时,分析了在高等植物中存在多种钾吸收和转运机制的可能原因。     

Recent advances in ascorbate biosynthesis and the physiological significance of ascorbate peroxidase in photosynthesizing organisms

Ascorbate (AsA), the most abundant water-soluble redox compound in plants and eukaryotic algae, has multiple functions. There is compelling genetic evidence that the biosynthesis of AsA proceeds via a D-mannose/L-galactose pathway and is the most significant source of AsA in plants. AsA plays important roles in antioxidative defense, particularly via the AsA/glutathione cycle. AsA peroxidase (APX) plays a central role in the cycle and is emerging as a key enzyme in cellular H(2)O(2) metabolism. Plants possess diverse APX isoenzymes in cellular compartments, including the chloroplast, cytosol, and microbody. In algae, however, the number and distribution of APX proteins are quite limited. Recent progress in molecular biological analysis of APX isoenzymes has revealed elaborate mechanisms for the tissue-dependent regulation of two chloroplastic APX isoenzymes by alternative splicing, and for redox regulation of cytosolic APX gene expression in response to light stress. Furthermore, transgenic plants overexpressing a chloroplastic APX isoenzyme enable us to evaluate the behavior of the enzyme under conditions of photo-oxidative stress. Molecular physiological analysis has revealed that cytosolic APX is part of the system modulating the cellular H(2)O(2) level in redox signaling.     

Class III peroxidases and ascorbate metabolism in plants

Class III peroxidases (PODs) have many functions in plant metabolism mainly dependent on their various physiological reducing substrates. Their involvement in plant differentiation and in the response against environmental stress is well known. Several evidences underline that ascorbate (ASC) levels affect POD reactions and, as a consequence, interfere with the metabolic pathways controlled by these isoenzymes. Ascorbate peroxidases (APXs), enzymes belonging to a different class of peroxidases (class I), are often present in the same cellular compartments in which PODs are also active. Since both APXs and PODs specifically utilise hydrogen peroxide as oxidising substrate they can compete, when co-present, for the same substrate. In this review, attention focuses on some of the physiological processes in which both ASC metabolism and PODs are involved. In particular, the scavenging of reactive oxygen species (ROS) during photosynthesis, cell elongation and wall stiffening as well as programmed cell death have been considered thoroughly. The relations between PODs and ASC metabolism have been discussed also in the attempt to outline their relevance for the correct plant development as well as for the perception/response of external stimuli allowing plants to cope with unfavourable conditions.     

Simulating ozone detoxification in the leaf apoplast through the direct reaction with ascorbate

 This paper presents a mathematical model which enables the semi-quantification of ozone (O₃) detoxification, based upon the direct reaction of the pollutant with ascorbate (ASC) located in the aqueous matrix associated with the cell wall (i.e. the apoplast). The model describes the uptake of ozone into the leaf and its direct reaction with ASC, taking into consideration the regeneration of dehydroascorbic acid in the cytosol, the rate of replenishment of cell wall ASC and the distribution of ASC between sub-cellular compartments – based upon the permeability of biomembranes to the neutral species, ascorbic acid and the pH of various sub-cellular compartments. The importance of various physico-chemical characteristics (e.g. stomatal conductance, mesophyll cell wall thickness and tortuosity, chloroplast volume, apoplast pH, ASC:O₃ reaction stoichiometry) in mediating the flux of ozone to the plasmalemma is analysed. Model simulations, supported by experimental observations, suggest that the ASC concentration in the leaf apoplast is high enough to scavenge a significant proportion of the O₃ taken up into the leaf interior, under environmentally relevant conditions. However, there is considerable variation between taxa in the potential degree of protection afforded by apoplastic ASC, emphasizing the need for an improved understanding of the reaction chemistry of O₃ in the cell wall. Received: 13 May 1999 / Accepted: 5 August 1999     

Plant mitochondria possess a short-patch base excision DNA repair pathway

Despite constant threat of oxidative damage, sequence drift in mitochondrial and chloroplast DNA usually remains very low in plant species, indicating efficient defense and repair. Whereas the antioxidative defense in the different subcellular compartments is known, the information on DNA repair in plant organelles is still scarce. Focusing on the occurrence of uracil in the DNA, the present work demonstrates that plant mitochondria possess a base excision repair (BER) pathway. In vitro and in organello incision assays of double-stranded oligodeoxyribonucleotides showed that mitochondria isolated from plant cells contain DNA glycosylase activity specific for uracil cleavage. A major proportion of the uracil–DNA glycosylase (UDG) was associated with the membranes, in agreement with the current hypothesis that the DNA is replicated, proofread and repaired in inner membrane-bound nucleoids. Full repair, from uracil excision to thymidine insertion and religation, was obtained in organello following import of a uracil-containing DNA fragment into isolated plant mitochondria. Repair occurred through single nucleotide insertion, which points to short-patch BER. In vivo targeting and in vitro import of GFP fusions showed that the putative UDG encoded by the At3g18 630 locus might be the first enzyme of this mitochondrial pathway in Arabidopsis thaliana.     

Regulation of TBK1 activity by Optineurin contributes to cell cycle-dependent expression of the interferon pathway

The innate immune system has evolved to detect and neutralize viral invasions. Triggering of this defense mechanism relies on the production and secretion of soluble factors that stimulate intracellular antiviral defense mechanisms. The Tank Binding Kinase 1 (TBK1) is a serine/threonine kinase in the innate immune signaling pathways including the antiviral response and the host defense against cytosolic infection by bacteries. Given the critical roles of TBK1, important regulatory mechanisms are required to regulate its activity. Among these, Optineurin (Optn) was shown to negatively regulate the interferon response, in addition to its important role in membrane trafficking, protein secretion, autophagy and cell division. As Optn does not carry any enzymatic activity, its functions depend on its precise subcellular localization and its interaction with other proteins, especially with components of the innate immune pathway. This review highlights advances in our understanding of Optn mechanisms of action with focus on the relationships between Optn and TBK1 and their implication in host defense against pathogens. Specifically, how the antiviral immune system is controlled during the cell cycle by the Optn/TBK1 axis and the physiological consequences of this regulatory mechanism are described. This review may serve to a better understanding of the relationships between the different functions of Optn, including those related to immune responses and its associated pathologies such as primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget’s disease of bone.     

查尔酮合成酶基因

查尔酮合成酶基因是苯丙氨酸代谢途径中的关键基因,在类黄酮类物质合成中扮演着重要的角色,调控着色素合成、防御反应、植物育性等生理生化过程,对植物的生长发育起着至关重要的作用。现对查尔酮合成酶在苯丙氨酸代谢途径中的地位、基因表达特性、基因功能以及基因进化等方面的进展做一介绍。     

Sphingolipids involvement in plant endomembrane differentiation: the BY2 case

Sphingolipids play an essential role in the functioning of the secretory pathway in eukaryotic organisms. Their importance in the functional organization of plant cells has not been studied in any detail before. The sphingolipid synthesis inhibitor fumonisin B1 (FB1), a mycotoxin acting as a specific inhibitor of ceramide synthase, was tested for its effects on cell growth, cell polarity, cell shape, cell cycle and on the ultrastructure of BY2 cells. We used cell lines expressing different GFP-tagged markers for plant cell compartments, as well as a Golgi marker fused to the photoconvertible protein Kaede. Light and electron microscopy, combined with flow cytometry, were applied to analyse the morphodynamics and architecture of compartments of the secretory pathway. The results indicate that FB1 treatment had severe effects on cell growth and cell shape, and induced a delay in cell division processes. The cell changes were accompanied by the formation of the endoplasmic reticulum (ER)-derived tubular aggregates (FB1-induced compartments), together with an inhibition of cargo transport from the ER to the Golgi apparatus. A change in polar localization of the auxin transporter PIN1 was also observed, but endocytic processes were little affected. Electron microscopy studies confirmed that molecular FB1 targets were distinct from brefeldin A (BFA) targets. We propose that the reported effects of inhibition of ceramide biosynthesis reflect the importance of sphingolipids during cell growth and establishment of cell polarity in higher plant cells, notably through their contribution to the functional organization of the ER or its differentiation into distinct compartments.     

Involvement of host regulatory pathways during geminivirus infection: a novel platform for generating durable resistance

Geminiviruses are widely distributed throughout the world and cause devastating yield losses in almost all the economically important crops. In this review, the newly identified roles of various novel plant factors and pathways participating in plant–virus interaction are summarized with a particular focus on the exploitation of various pathways involving ubiquitin/26S proteasome pathway, small RNA pathways, cell division cycle components, and the epigenetic mechanism as defense responses during plant–pathogen interactions. Capturing the information on these pathways for the development of strategies against geminivirus infection is argued to provide the basis for new genetic approaches to resistance.     

Control of the cell cycle.

Cell division is arguably the most fundamental developmental process for single-celled and multicellular organisms alike. The pathway from one cell division to the next is known as the cell cycle. A conserved biochemical regulatory network controls progress along this pathway in plants, animals, and yeasts. This review is intended to serve as a primer on the current state of the eukaryotic cell cycle regulatory model, an introduction to the special roles of cell division and its control in plant development, and a review of recent progress in applying the universal mitotic control paradigm to higher plant systems.