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Effects of delayed estrogen treatment and 20-HETE synthesis inhibition on postischemic pial artery response to acetylcholine in rats

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Open Journal of molecular and Integrative physiology 2014年第1期4卷 1-10页

作者： Chikao Miyazaki Emil N. Zeynalov Raymond C. Koehler Marguerite T. Littleton-Kearney Daniel K. Inouye Graduate School of Nursing Uniformed Services University of the Health Sciences Bethesda USA department of Anesthesiology/Critical Care Medicine School of Medicine Johns Hopkins University Baltimore USA

Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.

关键词： Hypoestrogenicity Estrogen Replacement Cerebral Ischemia/Reperfusion Cerebral Microvessels Estrogen Receptor Alpha 20-HETE HET0016

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乙烯诱导西瓜果实的水渍化败坏(英文)

植物生理与分子生物学学报 2004年第3期30卷 284-290页

作者：茅林春 Donald J Huber 浙江大学生物系统工程与食品科学学院 Horticultural Sciences department University of FloridaGainesvilleFL 32611USA

为了研究乙烯在西瓜(Citrullus ***)果实水渍化败坏过程中的作用,先将果实在5μL/L 1-甲基环丙烯(1-MCP)气体中处理18 h,然后在50 μL/L乙烯和20℃温度下贮藏。西瓜果实对乙烯处理的最初反应表现为胎座组织的电导率和游离汁液增加,同时... 详细信息

为了研究乙烯在西瓜(Citrullus ***)果实水渍化败坏过程中的作用,先将果实在5μL/L 1-甲基环丙烯(1-MCP)气体中处理18 h,然后在50 μL/L乙烯和20℃温度下贮藏。西瓜果实对乙烯处理的最初反应表现为胎座组织的电导率和游离汁液增加,同时出现组织软化和水渍化。水渍化的症状最初在靠近花萼端的内果皮中发生,在乙烯处理的第2天开始出现,ACC合成酶(ACS)和ACC氧化酶(ACO)的活性明显提高。1-MCP单独处理不产生任何明显的作用,但是会完全抑制外源乙烯诱导的水渍化败坏。没有经过乙烯处理的西瓜果实,贮藏2 d以后出现呼吸强度和乙烯释放量的高峰,10 d以后水渍化现象也零星出现。这些结果和1-MCP的预防效果说明,西瓜果实的水渍化败坏是一种由乙烯诱导的衰老现象。

关键词：水渍化乙烯 1-甲基环丙烯西瓜

PCBPs Regulate Circadian Rhythms

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PCBPs Regulate Circadian Rhythms

中国生物化学与分子生物学会2019年全国学术会议暨学会成立四十周年

作者： Ming Wang Yaling Wu Na Liu Dapeng Ju Musheng Zeng Erquan Zhang State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center National Institute of Biological Sciences department of Biochemistry Wannan Medical College

Circadian rhythms are endogenous, entrainable, rough 24 h oscillations that coordinate daily changes in physiology and behavior. These oscillations exist widely in most organisms and are controlled by the internal time-keeping systems called circadian clocks. The core mechanism of circadian clocks at the molecular level has been considered to be a transcription/translation feedback loop(TTFL) model which consists of positive and negative arms. In addition to the core TTFL loop, there are several additional loops. Period, amplitude and phase are three key properties of a circadian oscillator. From the data of a previous genome-wide RNAi screen, we identified poly(rC) binding proteins(PCBPs) as candidates for clock regulator. Our current study shows that PCBP1, PCBP4 can regulates the period of circadian clock, hnRNPK can induce the circadian clock of arrhythmic. So next,we plan to further investigate the detailed mechanism(s) on how PCBPs regulate the circadian rhythms.

关键词： circadian rhythms PCBP

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果蝇嗅觉分子机理研究进展

昆虫学报 2009年第7期52卷 799-807页

作者：吴仲南邹志华杜永均温州医学院健康与环境生态研究所浙江温州325035 department of Neuroscience and Cell Biology University of Texas Medical Branch301 University Blvd.

黑腹果蝇Drosophila melanogaster是生物学研究的重要模式生物,也是探索研究生物体嗅觉奥秘的理想材料。近年来,由于分子生物学技术在神经科学领域的广泛应用,黑腹果蝇嗅觉机理研究取得了许多重大突破,对气味分子受体及其识别机理、嗅... 详细信息

黑腹果蝇Drosophila melanogaster是生物学研究的重要模式生物,也是探索研究生物体嗅觉奥秘的理想材料。近年来,由于分子生物学技术在神经科学领域的广泛应用,黑腹果蝇嗅觉机理研究取得了许多重大突破,对气味分子受体及其识别机理、嗅觉神经电信号的产生和传递、嗅觉信息的加工、编码以及记忆等方面都有了深入的了解。研究表明,果蝇约1300个嗅神经元(olfactory receptor neurons,ORNs)共表达62种不同的气味受体蛋白(olfactory receptor proteins,ORs),用以检测和识别其所感受的所有化学气味分子。许多OR所识别的气味分子配体已鉴定出来,普通的气味(如水果的气味)由数种不同的OR组合来识别,而信息素(pheromone)分子则由单种特定的OR来检测。气味信息在嗅神经元内转换成神经电信号,嗅觉电信号沿嗅神经元的轴突传递到触角叶,再经投射神经元(projection neurons,PNs)将信息送至高级中枢如蘑菇体(mushroom body,MB)和侧角(lateral horn,LH),最终引发行为反应。在黑腹果蝇嗅觉信息传递通路中,某些蛋白如Dock,N-cadherin,Fruitless等起着重要作用,缺失这些蛋白会导致嗅觉异常。本文对这些研究进展作一综述。

关键词：果蝇嗅觉机理嗅觉编码嗅觉相关蛋白嗅觉受体

molecular and biochemical trajectories from diabetes to Alzheimer's disease: A critical appraisal

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World Journal of Diabetes 2015年第12期6卷 1223-1242页

作者： Rajat Sandhir Smriti Gupta department of Biochemistry Panjab University

Diabetes mellitus(DM), a metabolic disorder is a major orchestra influencing brain and behavioral responses via direct or indirect mechanisms. Many lines of evidence suggest that diabetic patients apparently face severe brain complications, but the story is far from being fully understood. Type 2 diabetes, an ever increasing epidemic and its chronic brain complications are implicated in the development of Alzheimer's disease(AD). Evidences from clinical and experimental studies suggest that insulin draws a clear trajectory from the peripheral system to the central nervous system. This review is a spot light on striking pathological, bio-chemical, molecular and behavioral commonalities of AD and DM. Incidence of cognitive decline in diabetic patients and diabetic symptoms in AD patients has brought the concept of brain diabetes to attention. Brain diabetes reflects insulin resistant brain state with oxidative stress, cognitive impairment, activation of various inflammatory cascade and mitochondrial vulnerability as a shared footprint of AD and DM. It has become extremely important for the investigators to understand the patho-physiology of brain complications in diabetes and put intensive pursuits for therapeutic interventions. Although, decades of research have yielded a range of molecules with potential beneficial effects, but they are yet to meet the expectations.

关键词： Diabetes mellitus Alzheimer's disease Insulin Type 2 diabetes Type 3 diabetes

A protocol for optical mapping of Ca2+ dynamics in murine sinoatrial preparation with optogenetic pacing

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A protocol for optical mapping of Ca2+ dynamics in murine si...

circadian clock circuitry in colorectal cancer

2019年中国生理学会心血管生理学术研讨会

作者： Ruirui Dong Razik Mu-u-min Christopher O'Shea Shicheng He Alastair Reith Kaizhong Duan Kun Kou Alexander Grassam-Rowe Xiaoqiu Tan Davor Pavlovic Xianhong Ou Ming Lei Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province Institute of Cardiovascular Research at Southwest Medical University department of Pharmacology University of Oxford

Among the animal models for studying the molecular basis of atrial and sinoatrial node（SAN） biology and disease,the mouse is a widely used species due to its handling and signaling proteins in the *** is therefore highly valuable to develop robust methodologies for studying SAN and atrial electrophysiological function in this ***,we describe a protocol for performing dual calcium-voltage optical mapping on mouse sinoatrial preparation（SAP）,in combination with an optogenetic approach,for studying SAP membrane potential,intracellular Ca2+transients,and pacemaker *** protocol includes the details for preparing an intact SAP,robust tissue dual-dye loading,light-programmed pacing,and high-resolution optical *** protocol provides an example of the use of the combination of optogenetic and optical mapping techniques for investigating SAP membrane potential and intracellular Ca2+transients and pacemaker activity with high temporal and spatial resolution in specific cardiac ***,our protocol provides a useful tool for studying SAP physiology and pathophysiology in mice.

关键词： sinoatrial node optogenetic pacing optical mapping murine heart

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World Journal of Gastroenterology 2014年第15期20卷 4197-4207页

作者： Gianluigi Mazzoccoli Manlio Vinciguerra Gennaro Papa Ada Piepoli department of Medical Sciences Division of Internal Medicine and Chronobiology UnitIRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"71013 San Giovanni Rotondo FoggiaItaly Istituto EuroMEditerraneo di Scienza e Tecnologia (IEMEST) 90100 PalermoItaly Division of Medicine Royal Free CampusInstitute for Liver and Digestive HealthUniversity College LondonLondon NW3 2PFUnited Kingdom department of Surgical Sciences Division of UrologyUniversity of Chieti66100 ChietiItaly department of Medical Sciences Research Laboratory and Division of GastroenterologyIRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"71013 San Giovanni Rotondo FoggiaItaly

Colorectal cancer is the most prevalent among digestive system *** relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and ***,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene *** of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer *** studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift *** this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.

关键词： Colorectal cancer Circadian rhythm Clock gene

Regulatory role of mitochondria in oxidative stress and atherosclerosis

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World Journal of Cardiology 2010年第6期2卷 150-159页

作者： Jui-Chih Chang Shou-Jen Kou Chin-San Liu department of Neurology Vascular and Genomic CenterChanghua Christian Hospital department of Surgery Changhua Christian Hospital

Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species(ROS)production,accumulation of mitochondrial DNA damage,and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptorγcoactivator(PGC-1),although more detailed mechanisms still need further *** on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochon- drial fusion-related protein(mitofusin),we thus infer the regulatory role of mitochondrial fusion/fission balance in AST *** this review,the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics,and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore,nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species(RNS)which act together with ROS to damage ***,in the second section we discuss mitochondrial ATP-sensitive K+ channels,which regulate mitochondrial ion transport to maintain mitochondrial physiology,involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases(CVD).Through this review,we can further appreciate the multi-regulatory functions of the mitochondria involved in AST *** understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria.

关键词： Apoptosis Atherosclerosis ATP-sensitive K+channels Free radical Mitochondrial biogenesis

Factors That Affect the Computational Prediction of Hot Spots in Protein-Protein Complexes

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Computational molecular Bioscience 2012年第1期2卷 23-34页

作者： Jianping Lin Pi Liu Hua-Zheng Yang Nagarajan Vaidehi College of Pharmacy Nankai University Tianjin China department of Immunology Beckman Research Institute of the City of Hope Duarte USA State Key Laboratory of Elemento-Organic Chemistry Elemento-Organic Chemistry Institute Nankai University Tianjin China

Protein-protein complexes play an important role in the physiology and the pathology of cellular functions, and therefore are attractive therapeutic targets. A small subset of residues known as “hot spots”, accounts for most of the protein-protein binding free energy. Computational methods play a critical role in identifying the hotspots on the proteinprotein interface. In this paper, we use a computational alanine scanning method with all-atom force fields for predicting hotspots for 313 mutations in 16 protein complexes of known structures. We studied the effect of force fields, solvation models, and conformational sampling on the hotspot predictions. We compared the calculated change in the protein-protein interaction energies upon mutation of the residues in and near the protein-protein interface, to the experimental change in free energies. The AMBER force field (FF) predicted 86% of the hotspots among the three commonly used FF for proteins, namely, AMBER FF, Charmm27 FF, and OPLS-2005 FF. However, AMBER FF also showed a high rate of false positives, while the Charmm27 FF yielded 74% correct predictions of the hotspot residues with low false positives. Van der Waals and hydrogen bonding energy show the largest energy contribution with a high rate of prediction accuracy, while the desolvation energy was found to contribute little to improve the hot spot prediction. Using a conformational ensemble including limited backbone movement instead of one static structure leads to better predicttion of hotpsots.

关键词： Hotspot Prediction Computational Mutagenesis Concoord Ensemble Protein-Protein Complexes