Transcriptional Regulation of Tyrosinase by α-synuclein and Inhibitors

酪氨酸酶（EC.1.14.18.1）是一种广泛存在于自然界中含铜的金属氧化酶，它具有单酚酶活性，可以将酪氨酸羟化形成L-多巴（L-DOPA），也具有二酚酶活力，将L-多巴氧化成多巴醌。它是生物形成黑色素合成的关键酶，决定了皮肤和头发色素的颜色。酪氨酸酶的异常表达引起了各种各样的皮肤病，如老年斑及光照损伤等。它还与人脑中的神经黑色素形成及神经退行性病变相关的帕金森病有关，因此酪氨酸酶抑制剂临床应用于与黑色素失调相关疾病的治疗。其在美白化妆品及日晒变黑应用方面具有重要作用。 本论文从天然植物中分离纯化出对酪氨酸酶具有很强抑制作用的抑制剂并探讨其对单酚酶和二酚酶活性的抑制作用机理。再以小鼠B16F...Tyrosinase (1.14.18.1), widely distributed in nature, is a metalloenzyme oxidase which catalyzes two distinct reactions of melanin synthesis---the hydroxylation of monophenol and the oxidation of o-diphenol to the corresponding o-quinone. It is a key enzyme in melanin biosynthesis, involved in determining the color of mammalian skin and hair. Its abnormal expression is responsible for the various ...学位：理学博士院系专业：生命科学学院生物化学与生物技术系_生物化学与分子生物学学号：2162006015333

Inhibitory mechanism of extracts from Ginkgo biolaba sarcotesta on mushroom tyrosinase

作者简介: 王勤(19692) ,女,山东济宁市人,博士,副教授,主要从事生物化学研究, (E-mail) qwang @xmu. edu. cn。 通讯作者(Author for correspondence ,E-mail :chenqx @xmu. edu. cn)[中文文摘] 以银杏外种皮为材料,采用水、乙醇和乙醇-乙醚三种不同的方法分离提取其中的活性物质(分别命名为1#,2#,3#),研究它们对蘑菇酪氨酸酶催化L-多巴(L-DOPA)氧化活力的影响。结果表明,这3种提取物均对蘑菇酪氨酸酶有抑制作用,1#,2#和3#对酶抑制作用的IC50分别为2.25、1.75和0.32mg/mL。抑制作用动力学结果表明:三种提取物对酶的抑制作用均表现为混合型,相应的抑制常数KI依次为2.11、1.62和0.29mg/mL;KIS依次为2.80、2.33和0.45mg/mL。结果显示,采用乙醇-乙醚提取的银杏外种皮提取物对酪氨酸酶抑制作用最强。[英文文摘] Three extractants(water,ethanol and ethanol-aether mixture)were isolated from Ginkgo biolaba sarcotesta,and then three kinds of extracts were used to test the inhibition on the activity of mushroom tyrosinase.The results showed that three extracts could inhibit the activity of tyrosinase obviously.The inhibitor’s concentration leading to 50% enzyme activity lost,IC50 was estimated to be 2.25,1.75 and 0.32 mg/mL,respectively.Their inhibition mechanisms were analyzed.All of three extracts showed reversibly inhibitors to tyrosinase and the type of inhibition belonged to be mixed-type.The inhibition constants,KI and KIS,of each extract were determined respectively and compared.The value of KI was determined to be 2.11,1.62 and 0.29 mg/mL,respectively;the value of KISwas determined to be 2.80,2.33 and 0.45 mg/mL,respectively.The ethanol-aether extracts showed the best inhibition on tyrosinase.福建省自然科学基金(B0510001);国家自然科学基金(30570408

巴戟天多糖的分离与纯化新方法

以巴戟天(Morinda officinalisHow)为原料,运用多种理化方法,提取纯化巴戟天粗多糖,经红外吸收光谱比较和鉴定确认提取物中有多糖特征吸收.采用苯酚—硫酸法测定多糖含量,以多糖的纯度和提取率为主要指标,对提取方法进行优化.结果表明,用乙醇-水提取法进行提取,用Sevag法除蛋白,氯化十六烷基吡啶(CPC)结合醇沉法进行纯化.正交实验结果表明提取纯化巴戟多糖最隹条件是乙醇浓度为85%,CPC浓度为0.4%,粗多糖浓度为10%的条件下,纯化多糖的纯度为89.7%,多糖的提取率为10.2%

4-氨基苯甲酸对蘑菇酪氨酸酶的抑制作用机理研究

报道了4-氨基苯甲酸(4-aminobenzoic acid)对蘑菇酪氨酸酶单酚酶和二酚酶活力的影响和抑制效应.结果表明,4-氨基苯甲酸对蘑菇酪氨酸酶的单酚酶和二酚酶活性均有抑制作用.导致单酚酶活力和二酚酶活力下降50%的抑制剂浓度(IC50)分别为0.35和0.30 mmol/L.4-氨基苯甲酸对单酚酶的迟滞时间有明显的延长效应,1.0 mmol/L可使单酚酶的迟滞时间从30.5 s延长到155.1 s,增加了4.4倍.4-氨基苯甲酸对二酚酶的抑制作用表现为混合型可逆抑制作用,抑制常数(KI和KIS)分别为0.259和1.46 mmol/L

条纹斑竹鲨鱼皮多肽对人永生化表皮角质形成细胞HaCAT生理生化活性的影响

通过细胞活力、增殖、迁移、细胞周期、胞内活性氧（ROS）和抗氧化能力的检测，分析条纹斑竹鲨（又称狗鲨，Chiloscyllium plagiosum）鱼皮多肽对人永生化表皮角质形成细胞（HaCAT细胞）的作用。实验结果显示：随着多肽作用浓度的增加，HaCAT细胞活力显著提升，最大达到144%；细胞单克隆增殖能力明显增强；细胞划痕迁移愈合速率增加；细胞周期无显著变化；胞内ROS显著降低，最低可达49.1%；在H2O2氧化损伤下细胞活力明显恢复，活力最高达到119%。上述结果表明条纹斑竹鲨鱼皮多肽对HaCAT细胞的多项生理生化活性具有促进作用，可为其开发作为功能性皮肤敷料提供理论依据。厦门海洋经济发展专项(17GYY011HJ05

闽南文化研究国际笔谈会论点选载

2013年12月21日,由闽南师范大学闽南文化研究院主办的“2013闽南文化研究国际笔谈会“在国际学术交流中心召开。来自海峡两岸及日本、新加坡等国家的闽南文化研究方面的专家、学者二十余人出席了会议。会议围绕着闽南文化的内涵、外延及特征,闽南文化的当代价值与社会功能,闽南文化研究的理论与方法,闽南文化的跨文化阐释,闽南文化的世界性及其意义,闽南文化与两岸交流,闽南文化的生态保护,闽南文化学科建设与人才培养等议题展开了深入的研讨,言简意赅,探幽发微,对当下闽南文化理论研究势必产生积极的影响。本期节录专家们的精彩发言,以飨读者,也希望由此来带动和促进闽南文化研究的进一步升华

Research on Preferred Stock: Disclosure,Motivation and Consequence

优先股是国内资本市场关注的热点问题,监管部门正在开展相应试点,对国外优先股相关问题的回顾和梳理对于我国开展优先股的实践和研究具有借鉴和启示作用。国外优先股研究主要从以下三方面开展:从发行主体、监管部门和投资者的角度探讨优先股的分类和信息披露;从税负动因、监管要求以及财务报表优化等角度分析优先股发行的动因;第三,从发行和回购的市场反应、长期市场表现等角度研究优先股的经济后果。The issuance of preferred stock is a hot issue in China's capital market.In this paper,we comprehensively review the relevant literature of preferred stock from three aspects.Firstly, we review the research on accounting classification and information disclosure of preferred stock from the perspectives of issuer, regulator and investor separately.Secondly, we review the relevant research on the motivations for issuing preferred stock,such as tax,regulatory and the optimization of financial reports.Finally,we review research on both short-term and long-term market reaction of the issuance and repurchase of preferred stock.上海高校青年教师培养资助计划(ZZLX12007); 上海立信会计学院创新创业教育实验基地项目(B8-3111-13-0501); 立信会计产学研基地项目(13GD02

The Inhibitory Effect on Mushroom Tyrosinase by the Extraction of the Inhibitor from the Outer Husk of Aloe vera

通讯作者:chenqx @xmu. edu. cn[中文文摘]以芦荟的表皮、同化薄壁组织和维管束组织为材料,经组织捣碎匀浆、石油醚萃取、过滤、旋转蒸发浓缩,得到芦荟皮酪氨酸酶抑制剂的提取物.研究该提取物对蘑菇酪氨酸酶的效应,结果表明,芦荟皮质部提取物对蘑菇酪氨酸酶有较强的抑制作用,其IC50值为0.439 mg/mL,抑制机理为可逆混合型.对其中的有效成分芦荟大黄素进行含量测定,结果为0.4%,说明芦荟大黄素在芦荟皮中占有相当的比例. [英文文摘] Mushroom Tyrosinase is an enzyme that is very important in the browning of fruit and vegetable.Browning of animal usually is caused by effect of Tyrosinase itself.The outer husk of aloe is separated to get the coarse inhibitor of Mushroom Tyrosinase by pounding to pieces,filtrating,extracting,distilling to concentrate liquid attained.We use this inhibitor to act with Mushroom Tyrosinase.Through this way,we can detect the influence of coarse inhibitor on Mushroom Tyrosinase(the rate of inhibit,the type of inhibit):the inhibitor′s concentration leading to 50% activity lost(IC50) of it was determined to be 0.439 mg/mL.The mechanism of this coarse extraction effecting on enzyme is reversible.The type of this coarse extraction effecting on enzyme is mixed type.The inhibition constant(KI) was determined to be 0.258 mg/mL.The KIS was determined to be 3.335 mg/mL.As to the major constitution of coarse inhibitor:Aloe-emodin,we detect the content of this compound is 0.4%.Through its structure,we can conclude that Aloe-emodin is the main compound which has strong influence on the activity of Mushroom Tyrosinase.国家自然科学基金(30570408) 和福建省重点科技项目 (2007N0051) 资

Emodin Attenuates The Neurotoxicity Induced by Nitric Oxide Through Inhibiting FOXO1 Transcriptional Activity

氧化应激所产生的活性氧和一氧化氮(nitric oxide,NO)自由基在心脑血管疾病、神经退行性疾病中发挥着重要作用,过量的NO可以导致自由基损伤,并诱导神经元的凋亡.大黄作为中医传统药物具有重要的药用价值,临床应用非常广泛.近年研究表明,大黄素具有抗氧化、免疫调节、抗菌、抗炎等功能,被广泛应用于肠道疾病、肾病、心血管疾病、胰腺炎等病症的治疗.Forkhead转录因子1(FOXO1)是Forkhead转录因子家族的一个重要成员,FOXO1对于胰岛素信号通路、DNA修复、清除活性氧损伤、细胞周期和凋亡的调控非常重要.而NO自由基对FOXO1的调控作用还不清楚,我们研究发现,NO的供体GSNO(亚硝基谷胱甘肽)或者L-Arg(L-精氨酸)可显著提高FOXO1的转录活性并促进其下游促凋亡基因Fas L、Bim的转录表达,进而诱导神经元死亡.我们进一步研究发现,大黄素可以通过降低FOXO1的转录水平以及蛋白质水平,缓解NO所诱导的神经元凋亡.该研究揭示了NO自由基诱导神经元损伤的新机制,同时也为了解大黄素的抗氧化作用提供了新的实验依据,对大黄素等中药有效成分的临床应用提供了重要参考.Reactive oxygen species(ROS) and NO free radicals generated from oxidative stress play an important role in the pathogenesis of neurodegenerative disease and cardiovascular and cerebrovascular diseases. Excessive NO production can cause free radical damage and induce neuron death. As one of the traditional Chinese medicine,Emodin have valuable and widely clinical applications. Recently, Emodin has been reported to have antioxidant,immunomodulatory, antibacterial, anti-inflamatory functions etc. FOXO1 is a vital member of the Forkhead family of transcription factors known to regulate the transcription of genes involved in cell cycle arrest, DNA repair in response to oxidative stress or apoptosis. However, it is unclear how the NO effect on FOXO1. In this study, we observed vital role of FOXO1 dependent transcriptional activation on neuronal death in response to Nitric oxide over-production. We found that NO donor GSNO or L-Arginine significantly increased the FOXO1 transcriptional activity, which induce the FOXO1 downstream proapoptotic genes(Fas L, Bim) expression and finally induce neuronal death. In addition, we screen natural Chinese herb extracts targets to regulating FOXO1 activity. Emodin shows dramatically effect in suppression of FOXO1 transcription activity and protein levels. What's more, Emodin can attenuate neuronal death induced by L-Arg. The current study first demonstrate that Nitric Oxide could regulate FOXO1 transcriptional activity to damage neuronal cell, which will benefit to deep understanding the neurotoxicity of NO free radical. Secondly, by Chinese herb extracts and antioxidants screen, we identified Emodin as one FOXO1 activity modulator which can attenuate neurotoxicity induced by NO. The current study will also provide a new insight for explaining the mechanisms of pathology of neurodegenerative disease and neuroprotective effects of Emodin

L-半胱氨酸作为化妆品美白添加剂的作用机理

酪氨酸酶(EC 1.14.18.1)是黑色素形成的关键酶,其抑制剂的研究是当前美白添加剂研究的热点.研究了L-半胱氨酸(L-Cys)对蘑菇酪氨酸酶和小鼠B16黑色素瘤细胞粗提的酪氨酸酶的抑制效应,实验结果表明,L-Cys对2种来源的酪氨酸酶有较强的抑制作用,其半效抑制浓度分别为1.75,15μmol/L.对小鼠B16黑色素瘤细胞粗提的酪氨酸酶的抑制主要表现为显著延长酶促反应的迟滞时间,同时显著降低酶的活力.进一步对L-Cys在细胞毒性方面进行了研究,结果表明,在200μmol/L浓度下,L-Cys对小鼠黑素瘤细胞B16的生长未显示出明显影响,对细胞状态、代谢MTT的能力、细胞增殖率等均无影响,无明显细胞毒性,是一种有潜力的增白剂,为L-Cys作为美白添加剂提供了依据