乙酰化修饰对人非组蛋白稳定性调控功能的最新进展

乙酰化修饰是一种广泛存在于生物体中的可逆性蛋白质翻译后修饰方式,主要发生于蛋白质赖氨酸残基的侧链NH2基团上,最早在组蛋白中发现。乙酰化修饰主要通过修饰组蛋白影响细胞的染色质结构以及激活细胞核内转录因子,从基因组水平来调控细胞的生命活动。随着乙酰化修饰检测技术和生物学研究的发展,发现乙酰化修饰也大量存在于非组蛋白中,并调控蛋白质的功能,进而影响多种生物学过程。其中,乙酰化修饰可以调控非组蛋白的稳定性,使其在细胞中更加稳定和持久地存在,这种调控机制在细胞的生长和分化等过程中具有重要作用,并影响多种疾病的发生发展。该文介绍了乙酰化修饰及其主要的生物学功能,系统总结了乙酰化修饰对人非组蛋白稳定性调控的机制与功能的影响,并介绍了乙酰化修饰调控蛋白质稳定性对疾病发生发展的作用,有助于解析疾病的发生机制,为疾病的治疗提供新的思路和方法。     

蛋白质构象病

蛋白质结构生物学既从蛋白质一级结构序列 ,也从蛋白质空间结构及其动态变化去研究蛋白质的性质和功能。生物医学研究表明蛋白质空间构象发生异常变化会引起疾病发生 ,形成了蛋白质构象病 (Ｐｒｏｔｅｉｎｃｏｎｆｏｒｍａ ｔｉｏｎａｌｄｉｓｅａｓｅｓ)这一新的病理学概念[1] 。1 .蛋白质构象病及其分子构象病理学一般讲 ,引起构象疾病的蛋白质分子与正常蛋白质同时存在于机体内 ,至少部分蛋白质具有正常折叠的空间构象 ,并以正常形态释放。当蛋白质构象异常变化时可导致其生物功能丧失 ,或者引起其后发生的蛋白质聚集与沉积 ,使组织结构…     

变异剪接体的结构、功能及其在疾病治疗中的应用

变异剪接(alternative splicing)是高等真核生物在发育和应激反应中调控基因表达的一种主要机制,能够调控蛋白表达,或产生编码具有不同功能蛋白的pre-mRNAs。剪接体(spliceosome)由五种snRNP(U1、U2、U4、U5和U6)和许多非snRNP蛋白质构成,参与整个剪接过程。变异剪接与诸多疾病有着密切联系,异常的变异剪接会导致疾病的发生,增加疾病的易感性与病变程度,甚至引起癌变。现就剪接体的生物学特征、剪接体与疾病的关系及其在疾病治疗方面的内容进行综述。     

糖基化蛋白质组学:结构、功能和研究方法

蛋白质糖基化修饰结构多样、分布广泛,以N-糖基化、O-Gal NAc糖基化和O-Glc NAc糖基化等不同修饰形式存在。糖修饰以各种方式广泛参与基本生物学过程,包括基因转录、蛋白质翻译、信号转导、细胞-细胞间以及宿主-病原体相互作用等。糖基化修饰的异常变化与多种重要疾病的发生发展相关,包括免疫性疾病、肿瘤、先天性糖缺陷等。该文系统展示几种常见糖修饰的结构、参与的生理病理过程,以及最新的研究方法,尤其是糖修饰蛋白质或肽段的特异性富集方法和基于质谱的序列分析方法进展,以期丰富糖修饰蛋白质的研究手段,为糖蛋白质功能机制研究、疾病治疗靶标或候选标志物的发现提供新视角。     

蛋白质的棕榈酰化修饰

棕榈酰化修饰是蛋白质翻译后脂质修饰的重要形式,是调控蛋白质的转运、稳定、定位和功能的重要机制,同时,棕榈酰化修饰还参与多种细胞生物学进程,与许多疾病的发生发展密切相关。本文主要就蛋白质棕榈酰化及其修饰酶与蛋白质功能、相关疾病的关系做一综述。     

长链非编码RNA在生物体中的调控作用

长链非编码RNA(Long non-coding RNA,lncRNA)的发现是基因组学和分子生物学研究领域的重要进展。lncRNA在生命活动中具有重要的调节功能,其表达紊乱与多种人类疾病的发生发展密切相关。研究表明,几乎所有的调控性lncRNA通过与不同种类的生物大分子,如DNA、RNA和蛋白质发生相互作用而行使其功能。文章概述了lncRNA在表观遗传学水平、转录水平及转录后水平调控基因表达的效应机制,并探讨了lncRNA如何在肿瘤发生和宿主防御过程中行使功能。不同于小分子ncRNA通过碱基互补配对调控靶基因的表达,大多数已鉴定的lncRNA通过调节蛋白质活性或维持蛋白质复合物的完整性发挥其生物学功能。因此,鉴定lncRNA-蛋白质相互作用可能是理解lncRNA功能的首要任务。     

长链非编码RNA与宫颈癌

长链非编码RNA (Long non-coding RNA,lncRNAs)是RNA的其中一员,其结构类似于mRNA,但由于没有保守的开放阅读框,因此不能编码蛋白质。LncRNAs曾被认为是基因转录后的异常现象或噪音,没有任何的生物学功能。随着研究的进一步深入,发现其可作为重要的调控分子参与人类正常或异常的生物学活动过程。LncRNAs与神经系统功能、机体代谢紊乱以及肿瘤等疾病的发生发展密切相关。异常表达于宫颈癌的lncRNAs通过发挥抑制肿瘤或促进肿瘤的作用,参与调控宫颈癌的各个生物学过程。文中结合最新报道就lncRNAs在宫颈癌的异常调节、分子调节机制和潜在临床应用方面进行综述。     

葡萄糖调节蛋白78的研究进展

葡萄糖调节蛋白78(glucose regulated protein 78 kD,GRP78)是位于内质网上的重要分子伴侣,在蛋白质折叠和转运过程及内质网应激反应中发挥重要作用。近年来发现,GRP78高表达与多种疾病发生发展密切相关,其生物学功能受到广泛关注。现综述国内外文献,对GRP78的生物学功能及与肿瘤、心血管疾病、糖尿病之间的关系进行分析与研究,为临床疾病治疗靶点提供理论依据。     

蛋白质翻译后修饰研究进展

翻译后修饰在蛋白质加工、成熟的过程中发挥着重要的作用,它可以改变蛋白质的物理、化学性质,影响蛋白质的空间构象、立体位阻及其稳定性,进而对蛋白质的生物学活性产生作用,引起蛋白质的功能改变。修饰基团自身的结构特性对蛋白质的性质、功能也会产生深远的影响。在已有的研究基础上,综述蛋白质翻译后修饰的主要类型以及各修饰作用潜在的生物学功能。     

环状RNA影响肝疾病的发生发展

环状RNA (circular RNA, circRNA)广泛存在于多种生物细胞中,是一类由3′末端和5′末端经反向剪接共价结合形成的RNA分子。circRNA具有保守性、结构稳定、组织细胞特异性表达等特征。它们具有调控基因转录、充当微RNA海绵、参与蛋白质翻译及充当蛋白质诱饵等重要生物学功能,可影响细胞的增殖、凋亡、周期、迁移、侵袭和上皮间质转化等过程。circRNA与病毒性肝炎、肝纤维化、肝细胞肝癌、脂肪性肝病等重要肝疾病的病理生理过程密切相关。鉴于肝疾病是我国最常见的一类重大疾病,本文总结了国内外关于circRNA影响肝疾病发生发展的机制,希望为预防、诊断和治疗肝疾病提供新思路。     

A/California/7/2009与A/California/4/2009病毒感染力比较

目的甲型H1N1流感病毒A/California/7/2009与A/California/4/2009病毒序列比较同源性在99%以上,本实验旨在比较两株病毒感染BALB/c小鼠研究感染力强弱。方法分别将A/California/7/2009（CA7）与A/California/4/2009（CA4）两株病毒分别连续10倍稀释后,对4~6周龄雌性BALB/c小鼠经乙醚麻醉后进行滴鼻攻毒,每个稀释度接种10只实验小鼠,测定CA7 MLD50为101.24/0.05 mL,检测小鼠感染、致病的多项指标,观察期为14 d。结果相同TCID50的CA7和CA4病毒感染小鼠,CA4感染小鼠后14 d内死亡率为20%,而CA7感染小鼠后8 d内死亡率为100%。CA7 106TCID50感染的小鼠病理表现为重度弥漫性间质性肺炎,CA4 106TCID50感染的小鼠病理表现为中度-重度间质性肺炎。结论在相同条件下,CA7感染力明显强于CA4。     

Ribonucieic Acid and Protein Metabolism of t12/t12 Embryos and T/t12 Spermatozoa

RNA precursor uptake and incorporation, amino acid uptake and incorporation, and the characterization of newly synthesized RNA and protein in pools of normal morulae and pools containing one-third t ¹²/ t ¹² morulae were compared. Maturing spermatoza of +/+ and T / t ¹² animals were analyzed for RNA and protein content, and the RNA characterized. No differences in these parameters could be ascribed to the t ¹² gene in homozygous embryos or haploid sperm.     

Comparison of parameters estimated from A/Ci and A/Cc curve analysis

The parameters estimated from traditional A/C _i curve analysis are dependent upon some underlying assumptions that substomatal CO₂ concentration (C _i) equals the chloroplast CO₂ concentration (C _c) and the C _i value at which the A/C _i curve switches between Rubisco- and electron transport-limited portions of the curve (C _i-t) is set to a constant. However, the assumptions reduced the accuracy of parameter estimation significantly without taking the influence of C _i-t value and mesophyll conductance (g _m) on parameters into account. Based on the analysis of Larix gmelinii’s A/C _i curves, it showed the C _i-t value varied significantly, ranging from 24 Pa to 72 Pa and averaging 38 Pa. t-test demonstrated there were significant differences in parameters respectively estimated from A/C _i and A/C _c curve analysis (p<0.01). Compared with the maximum ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) carboxylation rate (V_cmax), the maximum electron transport rate (J_max) and J_max/V_cmax estimated from A/C _c curve analysis which considers the effects of g _m limit and simultaneously fits parameters with the whole A/C _c curve, mean V_cmax estimated from A/C _i curve analysis (V_cmax-C _i) was underestimated by 37.49%; mean Jmax estimated from A/C _i curve analysis (J_max-C _i) was overestimated by 17.8% and (J_max-C _i)/(V_cmax-C _i) was overestimated by 24.2%. However, there was a significant linear relationship between V_cmax estimated from A/C _i curve analysis and V_cmax estimated from A/C _c curve analysis, so was it J_max (p<0.05).     

Comparative study of Bifidobacteriumanimalis, Escherichiacoli, Lactobacilluscasei and Saccharomycesboulardii probiotic properties

The present work investigates some probiotic properties of four different microorganisms (Bifidobacterium animalis var. lactis BB-12, Escherichia coli EMO, Lactobacillus casei and Saccharomyces boulardii). In vitro and in vivo tests were carried out to compare cell wall hydrophobicity, production of antagonistic substances, survival capacity in the gastrointestinal tract of germ-free mice without pathological consequence, and immune modulation by stimulation of Küpffer cells, intestinal sIgA and IL-10 levels. In vitro antagonism against pathogenic bacteria and yeast was only observed for the probiotic bacteria B. animalis and L. casei. The hydrophobic property of the cell wall was higher for B. animalis and E. coli EMO, and this property could be responsible for a better ability to colonize the gastrointestinal tract of germ-free mice. Higher levels of sIgA were observed mainly for S. boulardii, followed by E. coli EMO and B. animalis, and only S. boulardii induced a significant higher level of IL-10. In conclusion, for a probiotic use, S. boulardii presented better characteristics in terms of immunomodulation, and B. animalis and L. casei for antagonistic substance production. The knowledge of the different probiotic properties could be used to choice the better microorganism depending on the therapeutic or prophylactic application.     

C-Glycosylflavones and xanthones in leaves of Rigidella,sessilanthera and Fosteria

Four New World genera are included in the tribe tigrideae of the Iridaceae. These genera, which have been the subject of recent systematic treatments [1–4], share many characteristics; e.g. a haploid complement of two large and 12 small chromosomes and bisulcate pollen grains. However, the taxonomic and phyletic relationships within and between these genera have been based strictly on floral morphology and may simply reflect the primary pollinators of these genera [4,5].The flavonoid chemistry of eight species in three of the four genera, Rigidella, Sessilanthera and Fosteria, was investigated as part of a systematic study of Tigrideae. Our results are summarized in Table 1 nad Fig. 1. Although a recurrent pattern of $\text{C-}\text{glycosylflavones}$ and xanthones characterize the leaves of these taxa, each species exhibits a distinctive array of compounds. The same classes of compounds occur in other tribes of the Iridaceae: $\text{C-}\text{glycosylflavones}$ occur in the Irideae [6,7], Cipureae, and Mariceae and xanthones in Irideae [6] and Sisyrinchieae [6].     

cis- and trans-phytoene in Verticillium agaricinum

cis-Phytoene and trans-phytofluene were identified in illuminated cultures of Verticillium agaricinum in addition to the other carotenoids     

Alkylation of isolated chromatin with N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea

When isolated chromatin is incubated with the carcinogens N-methyl-N-nitrosourea (MeNU) and N-ethyl-N-nitrosourea (EtNU), DNA and chromosomal proteins become alkylated to increasingly greater extents as the carcinogen concentrations increase. With either MeNU or EtNU, the core and linker DNA of chromatin are alkylated to essentially identical extents. Alkylation of chromatin DNA as well as free DNA is drastically reduced at physiological ionic strengths (e.g. 0.15 M NaCl). The presence of 0.15 M NaCl, on the other hand, enhances alkylation of chromosomal proteins. While EtNU is much less reactive to DNA than MeNU, alkylation of chromosomal proteins relative to that of chromatin DNA has been found to be markedly greater with EtNU than with MeNU. Such a difference in their relative reactivities toward DNA and proteins may be related to the known difference of carcinogenic potency between these N-nitroso compounds.     

Effects of NH+4-N and NO+3-N on growth and metabolism of Sphagnum magellanicum

Photosynthetic CO₂-fixation, chlorophyll content, growth rate and nitrate reductase activity were used to examine the influence of NH⁺₄-N and NO⁻₃-N on Sphagnum magellanicum cultivated under defined conditions in phytotrons. NO⁻₃-concentrations up to 322 μ M were found to be favourable. Increased NH⁺₄ concentrations, however, resulted in growth inhibition and decreased chlorophyll content at concentrations ≧ 255 μ M ; e.g. 600 μ M NH⁺₄ caused a 20% reduction of nitrate reductase activity and net photosynthesis. For raised bog Sphagna an improved standard nutrient solution is proposed with the following ion concentrations (μ M ): 55 Na⁺; 17 K⁺; 95 NH⁺₄; 22 Ca²⁺; 22 Mg²⁺; 2 Fe³⁺; 20 Cl⁻; 100 NO⁻₃; 57 SO^2-₄; 7.4 H₂PO⁻₄; trace elements: A-Z solution (Hoagland) 50 μl 1000 ml⁻¹; pH 5.8.     

Nδ-acetylornithine and S-methylcysteine in blood plasma

N^δ-Acetylornithine and S-methylcysteine have been identified as minor components of deproteinized blood plasma of human and bovine blood. Human blood plasma contains a variable amount of acetylornithine, averaging 1.1 ± 0.4 μmol/l (range 0.8–0.2 μmol/l). Urine contains a very small amount of acetylornithine, approximately 1 nmol/mg creatinine (1 μmol/day). Human blood plasma contains 3.9 ± 1.9 μmol/l (range 1.4–6.5 μmol/l) of S-methylcysteine. Urine contains approximately 5 nmol/mg creatinine; after acid hydrolysis the amount is increased to 20 nmol/mg creatinine.