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Fibronectin: Functional character and role in alcoholic liver disease

World Journal of Gastroenterology 2011年第20期17卷 2482-2499页

作者： Razia S Aziz-Seible carol a casey Department of Biomedical Sciences Creighton University Department of Biochemistry and Molecular Biology University of Nebraska Medical Center985870 Nebraska Medical Center Department of Internal Medicine University of Nebraska Medical Center 986350 Nebraska Medical Center The Liver Study Unit Omaha Veterans Affairs Medical Center

Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this r

关键词： Fibronectin Liver disease Alcoholic liver disease Endocytosis Cellular fibronectin

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Impact of asialoglycoprotein receptor deficiency on the development of liver injury

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World Journal of Gastroenterology 2009年第10期15卷 1194-1200页

作者： Serene ML Lee carol a casey Benita L McVicker Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States Liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

The asialoglycoprotein （ASGP） receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis （RME）. The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease （ALD）. The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice （lacking a functional ASGP receptor） to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas （CD95） antibody, carbon tetrachloride （CCh） and lipopolysaccharide （LPS）/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

关键词： Asialoglycoprotein receptor Asialoglycoproteinreceptor deficient mice Receptor-mediatedendocytosis Alcohol Carbon tetrachloride Anti-Fas Lipopolysaccharide/galactosamine Toxicant-induced liverinjury

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Effect of ethanol on pro-apoptotic mechanisms in polarizedhepatic cells

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World Journal of Gastroenterology 2007年第37期13卷 4960-4966页

作者： Benita L McVicker Dean J Tuma carol a casey Liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol- induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system.

关键词： Hepatoma hybrid cells Ethanol Apoptosis Fas receptor Caspase

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Cellular fi bronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury

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World Journal of Hepatology 2011年第2期3卷 45-55页

作者： Razia S Aziz-Seible Benita L McVicker Kusum K Kharbanda carol a casey Department of Biochemistry and Molecular Biology University of Nebraska Medical Center985870Nebraska Medical CenterOmahaNE68198-5870United States Liver Study Unit Omaha Veterans Affairs Medical Center4101 Woolworth AvenueOmahaNE68105United States

AIM:To examine the consequences of cellular f ibronectin(cFn)accumulation during alcohol-induced injury,and inv estigate whether increased cFn could have an effect on hepatocytes(HCs)by producing factors that could cont ribute to alcohol-induced liver ***:HCs were isolated from rats fed a control or ethanol liquid diet for four to six *** c Fn(up to 7.5 μg/mL)was added to cells cultured for 20 h,and viability(lactate dehydrogenase),apoptosis(caspase activity)and se cretion of proinflammat-ory cytokines(tumor ne c rosis fac tor alpha,TNF-α and interleukin 6,IL-6),mat rix metalloproteinases(MMPs)and their inhibitors(tissue inhibitors of metall-oproteinases,TIMPs)was det *** ation of iodinated cFn was det ermined over a 3 h time period in the ***:cFn degradation is impaired in HCs isolated from ethanol-fed animals,leading to its accumulation in the *** of exogenous cFn did not affect viability of HCs from control or ethanolfed animals,and apoptosis was affected only at the higher *** retion of MMPs,TIMPs,TNF-α and IL-6,however,was increased by exogenously added cFn,with HCs from ethanolfed animals showing increased susceptibility compared to the ***:These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage.

关键词： Alcoholic liver diseases Hepatocytes Fibronectin Asialoglycoprotein receptor Inflammation Fibrosis

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因特网的分析索引:乌托邦的梦想

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图书馆杂志 2000年第6期19卷 13-17页

作者：祝力 carol casey 解放军外国语学院图书馆河南洛阳471003 美国拉法耶特市路易斯安那大学杜波图书馆编目部

检索互无关联的信息条目和数字内容时,所有查询因特网资源的方法都变得力不从心。本文通过研究现有的因特网查询方法、传统的书目控制和网站设计,探讨了对分析索引的需求问题。通过对这些索引的开发、设计和资源筛选过程中遇到的相关问... 详细信息

检索互无关联的信息条目和数字内容时,所有查询因特网资源的方法都变得力不从心。本文通过研究现有的因特网查询方法、传统的书目控制和网站设计,探讨了对分析索引的需求问题。通过对这些索引的开发、设计和资源筛选过程中遇到的相关问题的讨论,得出一个结论,即在因特网上创建全面的分析索引不现实,而创建小型具体化的索引可能是查询某些具体数字信息的最佳途径。

关键词：因物网分析索引书目控制网上信息

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北极海底嗜热菌的多样性及其对深海油气勘探的指示意义

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海洋地质 2010年第1期26卷 24-27,9页

作者： casey Hubert Alexander Loy Maren Nickel carol Arnosti 施秋华（译）万志峰（译）

微生物曾多次被发现存在于那些并不利于它们新陈代谢的环境中，其来源与分布一直有待进一步研究。例如，在北极地区的海底恒冷的海洋沉积物中，发现了大量嗜热菌的存大，并通过实验估算出，平均每年每平方米有超过108嗜热菌孢子沉积。... 详细信息

微生物曾多次被发现存在于那些并不利于它们新陈代谢的环境中，其来源与分布一直有待进一步研究。例如，在北极地区的海底恒冷的海洋沉积物中，发现了大量嗜热菌的存大，并通过实验估算出，平均每年每平方米有超过108嗜热菌孢子沉积。在低温条件下，它们并不显示出明显的活性，但通过水解作用和发酵作用，它们能迅速矿化有机质。值得一提的是，与这类细菌亲源关系比较近的种系多存在于地下温暖的油藏区和洋壳生态系统中，因此，了解它们的来源、分布机制及其多样性对于深海油气的寻找在一定程度上具有指示意义。

关键词：油气勘探北极地区嗜热菌多样性深海海底海洋沉积物新陈代谢

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