硒蛋白S与2型糖尿病

硒是哺乳动物不可缺少的微量元素,在人体内通过硒蛋白形式发挥多种生物学功能。早期的研究证实硒具有胰岛素样作用,补硒或硒蛋白可预防和治疗2型糖尿病(type 2 diabete mellitus, T2DM)。硒蛋白S (Selenoprotein S, SelS)参与机体内质网相关降解通路、氧化应激、炎症反应,并对血糖、血脂具有调控作用;同时,SelS异常表达于T2DM患者体内,参与胰岛素抵抗,并诱发血管病变。该文综述硒蛋白S基因的表达调控、生物学作用、代谢调节,以及与T2DM相关的研究,为T2DM的治疗提供理论依据。     

Glutathione-complexed [2Fe-2S] clusters function in Fe–S cluster storage and trafficking

Glutathione-coordinated [2Fe-2S] complex is a non-protein-bound [2Fe-2S] cluster that is capable of reconstituting the human iron-sulfur cluster scaffold protein IscU. This complex demonstrates physiologically relevant solution chemistry and is a viable substrate for iron-sulfur cluster transport by Atm1p exporter protein. Herein, we report on some of the possible functional and physiological roles for this novel [2Fe-2S](GS₄) complex in iron-sulfur cluster biosynthesis and quantitatively characterize its role in the broader network of Fe–S cluster transfer reactions. UV–vis and circular dichroism spectroscopy have been used in kinetic studies to determine second-order rate constants for [2Fe-2S] cluster transfer from [2Fe-2S](GS₄) complex to acceptor proteins, such as human IscU, Schizosaccharomyces pombe Isa1, human and yeast glutaredoxins (human Grx2 and Saccharomyces cerevisiae Grx3), and human ferredoxins. Second-order rate constants for cluster extraction from these holo proteins were also determined by varying the concentration of glutathione, and a likely common mechanism for cluster uptake was determined by kinetic analysis. The results indicate that the [2Fe-2S](GS₄) complex is stable under physiological conditions, and demonstrates reversible cluster exchange with a wide range of Fe–S cluster proteins, thereby supporting a possible physiological role for such centers.     

H_2S与急性肺损伤研究进展

<正>急性肺损伤是一种过度炎症反应,它是在感染、创伤等过程中导致的一种过度炎性反应,严重时则被称为急性呼吸窘迫综合征。多年来,急性肺损伤一直是临床常见的严重疾病,急性肺损伤的发病机制也未完全阐明。大量研究证明,继NO和CO之后的第3种信号分子H2S是重要的信使分子,并具有血管功能调节的作用。还有研究证明,H2S具有多方面的生物学作用,如参与低氧性肺动脉高压和感染性休克以及减轻兴奋性氨基酸对神经元的毒性作用等。内源性     

H_2O_2介导H_2S诱导的拟南芥气孔关闭

以拟南芥（Arabidopsis thaliana）为材料,研究了过氧化氢（H2O2）在硫化氢（H2S）调控气孔运动信号转导中的作用。结果表明,光下H2S的供体硫氢化钠（NaHS）能够诱导拟南芥气孔关闭;且能够显著提高叶片和保卫细胞胞质H2O2含量;H2O2的清除剂AsA和H2O2合成酶的抑制剂可不同程度地抑制NaHS诱导的拟南芥气孔关闭及叶片和保卫细胞胞质H2O2水平的升高;NaHS对AtrbohD、AtrbohF、Atpao2和Atpao4突变体气孔关闭、叶片和保卫细胞胞质H2O2水平升高的诱导作用要明显的小于野生型,但对AtPAO2和AtPAO4过表达株系叶片和保卫细胞H2O2水平的升高较野生型显著。据此推测,来源于NADPH氧化酶、细胞壁过氧化物酶和多胺氧化酶途径的H2O2参与H2S诱导的拟南芥气孔关闭。     

pH dependent stabilization of S2QA − and S2QB − charge pairs studied by thermoluminescence

The pH dependence of emission peak temperature and decay time of thermoluminescence arising from S₂Q_B ^– and S₂Q_A ^– recombinations demonstrates that a stabilization of S₂Q_B ^– occurs at low pH whereas stabilization of S₂Q_A ^– occurs at high pH. Based on comparative analysis of thermoluminescence parameters of the two types of recombination, we suggest that in the pH range between 5.3 and 7.5, E_m(S₂/S₁) and E_m(Q_A/Q_A ^–) are constant, but E_m(Q_B/Q_B ^–) gradually increases with decreasing pH, while in the pH range between 7.5 and 8.5, an unusual change occurs on S₂Q_A ^– charge pair, which is interpreted as either a decrease in E_m(S₂/S₁) or an increase in E_m(Q_A/Q_A ^–).     

H2S人工诱导小鼠冬眠成功

H2S是一种公认的毒性气体,但最近发现其是神经、心血管等系统功能调节的新型气体信号分子。BlackstoneE等在Science杂志上报道:将小鼠暴露于80ppm(80mg/m3)的H2S中,五分钟小鼠的氧消耗下降50%,CO2的排出量下降60%,暴露6小时,代谢率下降90%,中心体温下降到比周围环境温度高2℃。在最低体温时,CO2的排出量及氧的消耗仅为正常时的10%,且小鼠的呼吸频率从120次/分降到10次/分。将小鼠暴露于不同浓度的H2S(0ppm～80ppm),H2S呈浓度依赖性抑制中心体温,且代谢率的降低不依赖于周围环境的温度。在80ppm的H2S条件下暴露6小时后回到正常环境下,…     

SARS-CoV-2 S蛋白:研究进展与挑战

SARS-CoV-2是一种新暴发的能在人际之间快速传播并造成大流行的病原体。冠状病毒表面的刺突蛋白(S)在决定病毒宿主特异性、致病性和种间传播方面有着重要影响,亦是研发SARS-CoV-2疫苗的最重要抗原蛋白和开发抗病毒药物的重要靶点,因此,S蛋白是SARS-CoV-2暴发后研究最多的SARS-CoV-2蛋白。本文就SARSCoV-2 S蛋白的最新研究进展进行综述,并就目前研究面临的问题和挑战加以讨论。     

WEB2基因参与酿酒酵母S期检查点调控

WEB2基因编码产物为一种DNA解链酶。WEB2突变株经hydroxyurea阻断DNA合成后,经流式细胞仪检测DNA含量、纺锤体微管间接免疫 荧光染色及存活率测定,结果显示WEB2突变株表现S期检查点缺失。推测WEB2除了具有解链酶作用外,还参与酿酒酵母S期检查点调控机制,位于已建立的S期检查点信号传导通路模型上。本研究有助于加深对真核细胞检查点调控的了解,为研究肿瘤的发生机制提供线索。     

HIV-1 Protease Uses Bi-Specific S2/S2′ Subsites to Optimize Cleavage of Two Classes of Target Sites

Retroviral proteases (PRs) have a unique specificity that allows cleavage of sites with or without a P1′ proline. A P1′ proline is required at the MA/CA cleavage site due to its role in a post-cleavage conformational change in the capsid protein. However, the HIV-1 PR prefers to have large hydrophobic amino acids flanking the scissile bond, suggesting that PR recognizes two different classes of substrate sequences. We analyzed the cleavage rate of over 150 combinations of six different HIV-1 cleavage sites to explore rate determinants of cleavage. We found that cleavage rates are strongly influenced by the two amino acids flanking the amino acids at the scissile bond (P2–P1/P1′–P2′), with two complementary sets of rules. When P1′ is proline, the P2 side chain interacts with a polar region in the S2 subsite of the PR, while the P2′ amino acid interacts with a hydrophobic region of the S2′ subsite. When P1′ is not proline, the orientations of the P2 and P2′ side chains with respect to the scissile bond are reversed; P2 residues interact with a hydrophobic face of the S2 subsite, while the P2′ amino acid usually engages hydrophilic amino acids in the S2′ subsite. These results reveal that the HIV-1 PR has evolved bi-functional S2 and S2′ subsites to accommodate the steric effects imposed by a P1′ proline on the orientation of P2 and P2′ substrate side chains. These results also suggest a new strategy for inhibitor design to engage the multiple specificities in these subsites.     

一株类胡萝卜素高产菌S2的研究

从废水中分离到一株球形红杆菌Ｓ２,能够在光照微氧条件下以葡萄糖为碳源,脲为氮源的培养基上旺盛生长,并产生大量红色胞内类胡萝卜素。在最适合条件下,经３８ｈ分批发酵,类胡萝卜素产量达３１２ｍｇ／Ｌ。     

H2S在植物抗逆中的作用研究进展

综述了H2S在植物体内的产生途径及其在植物抗逆中的作用。越来越多的证据表明在动物体内,H2S是人们发现的第3种气体信号分子,但对植物体内的H2S的研究较少。     

中枢神经系统H2S的作用及机制研究进展

中枢神经系统内源性硫化氢 (H2 S)主要由胱硫醚 β 合酶合成。脑内H2 S对中枢神经系统多种生理和病理过程有重要的影响 :(1)H2 S通过cAMP途径 ,易化海马长时程增强的产生 ;(2 )H2 S通过下丘脑 垂体 肾上腺轴来参与神经内分泌功能的调节 ;(3)H2 S协同一氧化氮松弛脑血管平滑肌 ,从而调节血压。此外 ,H2 S还与脑血管损害、多种遗传性疾病的脑功能障碍有关     

SARS冠状病毒S蛋白的功能性受体-ACE2

SARS冠状病毒的棘突S蛋白 ,与细胞受体介导的感染有关。血管紧张素转化酶 2 (ACE2 )是SARS CoVS蛋白的功能性受体 ,人类ACE2酶的细胞外区域由 2个亚基组成 ,其中锌金属肽酶区域可以进一步分成 2个亚域 (I和II) ,形成一个长而深的裂缝 ,环绕裂缝顶端的隆起线可能作为与S 糖蛋白结合的区域。ACE2可以与SARS CoVS蛋白的S3 1 8 5 1 0结合。这将为发展新型SARS疫苗和SARS的预防和治疗提供新的研究方向。     

H2O2介导的H2S产生参与干旱诱导的拟南芥气孔关闭

以野生型拟南芥(Arabidopsis thaliana)及其突变体(atrbohD、atrbohF、atrbohD/F、atl-cdes、atd-cdes)和过表达株系(OEL-CDes、OED-CDes)为材料, 利用药理学实验, 结合分光光度法和激光共聚焦显微技术, 探讨硫化氢(hydrogen sulfide, H₂S)在干旱诱导的拟南芥气孔关闭中的作用及其与过氧化氢(hydrogen peroxide, H₂O₂)的关系。结果表明, H₂S清除剂次牛磺酸(hypotaurine, HT)及合成抑制剂氨氧基乙酸(aminooxy acetic acid, AOA)、羟胺(hydroxylamine, NH₂OH)和丙酮酸钾(potasium pyruvate, C₃H₃KO₃)+氨水(ammonia, NH₃)均可不同程度抑制干旱诱导的气孔关闭; 干旱对OEL-CDes和OED-CDes植株气孔关闭的诱导作用明显, 而atl-cdes和atd-cdes叶片气孔对干旱胁迫反应的敏感性下降; 干旱胁迫能明显增加拟南芥保卫细胞中H₂O₂水平及叶片中H₂S含量, 提高D-/L-半胱氨酸脱巯基酶活性及基因表达量, 而对突变体atrbohD、atrbohF和atrbohD/F没有显著影响。清除H₂O₂可减弱干旱胁迫对H₂S含量和D-/L-半胱氨酸脱巯基酶活性的诱导效应。研究 结果表明H₂S位于H₂O₂下游参与干旱诱导拟南芥气孔关闭的信号转导过程。     

H2O2介导的H2S产生参与干旱诱导的拟南芥气孔关闭

以野生型拟南芥(Arabidopsis thaliana)及其突变体(atrbohD、atrbohF、atrbohD/F、atl-cdes、atd-cdes)和过表达株系(OEL-CDes、OED-CDes)为材料,利用药理学实验,结合分光光度法和激光共聚焦显微技术,探讨硫化氢(hydrogen sulfide,H2S)在干旱诱导的拟南芥气孔关闭中的作用及其与过氧化氢(hydrogen peroxide,H2O2)的关系.结果表明,H2S清除剂次牛磺酸(hypotaurine,HT)及合成抑制剂氨氧基乙酸(aminooxy acetic acid,AOA)、羟胺(hydroxylamine,NH2OH)和丙酮酸钾(potasium pyruvate,C3H3KO3)+氨水(ammonia,NH3)均可不同程度抑制干旱诱导的气孔关闭;干旱对OEL-CDes和OED-CDes植株气孔关闭的诱导作用明显,而atl-cdes和atd-cdes叶片气孔对干旱胁迫反应的敏感性下降;干旱胁迫能明显增加拟南芥保卫细胞中H2O2水平及叶片中H2S含量,提高D-/L-半胱氨酸脱巯基酶活性及基因表达量,而对突变体atrbohD、atrbohF和atrbohD/F没有显著影响.清除H2O2可减弱干旱胁迫对H2S含量和D-/L-半胱氨酸脱巯基酶活性的诱导效应.研究结果表明H2S位于H2O2下游参与干旱诱导拟南芥气孔关闭的信号转导过程.     

基于生物信息学分析SARS-CoV-2 S蛋白与ACE2受体结合机制

[目的]预测并分析ACE2受体与SARS-CoV-2S蛋白结合的机制.[方法]从NCBI数据库中获取S蛋白及ACE2蛋白的氨基酸序列,利用在线软件分析其理化性质、高级结构及功能域,通过STRING软件构建ACE2蛋白相互作用网络,分析其关联通路和代谢途径.[结果]S蛋白由1 273个氨基酸组成,与SARS-COVS蛋白...     

Ca2+位于H2O2上游参与H2S诱导的拟南芥气孔关闭过程

以拟南芥为材料,利用药理学实验,结合分光光度法和激光共聚焦显微技术,研究了Ca2+在硫化氢(H2S)诱导拟南芥气孔关闭过程中的作用及其与过氧化氢(H2O2)的关系。结果表明： H2S诱导气孔关闭, Ca2+螯合剂EGTA和质膜Ca2+通道阻断剂硝苯地平(Nif)能不同程度抑制H2S诱导的气孔关闭,而内质网钙泵阻断剂毒胡萝卜素(Thaps)对H2S的作用无显著影响。由此推测, Ca2+参与调节H2S诱导的拟南芥气孔关闭过程,且胞质中Ca2+来源于胞外Ca2+的内流。另外, H2S诱导拟南芥叶片NADPH氧化酶基因AtRBOHD和AtRBOHF以及细胞壁过氧化物酶基因AtPRX34表达增强,促进叶片和保卫细胞中H2O2积累, EGTA对此起抑制作用,而外源CaCl2处理上调AtRBOHD、AtRBOHF和AtPRX34的表达。表明Ca2+可能位于H2O2上游参与H2S诱导的拟南芥气孔关闭过程。