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The consequences of CAT2 arginine tr...

Manner, Cathyryne Kapiolani.

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The consequences of CAT2 arginine transporter ablation in cancer and neuropathology.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The consequences of CAT2 arginine transporter ablation in cancer and neuropathology./
作者:	Manner, Cathyryne Kapiolani.
面頁冊數:	150 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2042.
Contained By:	Dissertation Abstracts International64-05B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3091320
ISBN:	049639035X

The consequences of CAT2 arginine transporter ablation in cancer and neuropathology.
Manner, Cathyryne Kapiolani.

The consequences of CAT2 arginine transporter ablation in cancer and neuropathology. - 150 p.

Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2042.

Thesis (Ph.D.)--University of California, San Diego, 2003.

Nitric oxide (NO) is produced from arginine by the NO synthase (NOS) enzymes. NOS2, which requires extracellular arginine for NO synthesis, is co-induced with cationic amino acid transporter 2 (CAT2) in many activated cell types and is involved in the pathogenesis of both cancer and neurological disease. Genetic ablation of Cat2 provided the essential tool to characterize the role of this transporter in the regulation of NO production and the development and progression of mouse models of breast cancer and multiple sclerosis (MS). These aims were accomplished by measuring the capacity of specific cell types to produce NO in vitro, and by examining disease phenotypes in vivo.

ISBN: 049639035XSubjects--Topical Terms:

1017719
Biology, Molecular.

The consequences of CAT2 arginine transporter ablation in cancer and neuropathology.
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245 1 4 $a The consequences of CAT2 arginine transporter ablation in cancer and neuropathology.
300 $a 150 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2042.
500 $a Chair: Carol L. MacLeod.
502 $a Thesis (Ph.D.)--University of California, San Diego, 2003.
520 $a Nitric oxide (NO) is produced from arginine by the NO synthase (NOS) enzymes. NOS2, which requires extracellular arginine for NO synthesis, is co-induced with cationic amino acid transporter 2 (CAT2) in many activated cell types and is involved in the pathogenesis of both cancer and neurological disease. Genetic ablation of Cat2 provided the essential tool to characterize the role of this transporter in the regulation of NO production and the development and progression of mouse models of breast cancer and multiple sclerosis (MS). These aims were accomplished by measuring the capacity of specific cell types to produce NO in vitro, and by examining disease phenotypes in vivo.
520 $a Cat2 knockout mice were healthy and fertile, with a normal lifespan, suggesting that CAT2 is dispensable for these physiological parameters. Nevertheless, NOS2-mediated NO production was significantly reduced in cultured macrophages and astrocytes from Cat2-/- mice. In contrast, NOS2 function was only mildly impaired in Cat2-/- fibroblasts, indicating that cells differ in their dependence on CAT2 for NOS2 activity and that the phenotype of Cat2-/- mice may not be predictable from the results of experiments with Nos2 -/- mice.
520 $a NOS2 has important, yet still controversial, functions in cancer growth and metastasis. The effects of Cat2 and Nos2 deficiency were characterized and compared in a transgenic model of breast cancer. Although the findings were not statistically significant, the data indicated that CAT2 might promote tumor growth and inhibit metastasis. NOS2 stimulated tumorigenesis and metastatic dissemination in a mixed FvB-C57B1/6 genetic background, but had no effect in a pure FvB strain.
520 $a NO exhibits both protective and destructive effects in experimental allergic encephalomyelitis (EAE), an animal model of MS. Although Nos2 deficiency exacerbated the clinical course of active EAE, Cat2 deficiency delayed disease onset and reduced incidence. The precise mechanisms have not yet been elucidated, but Cat2 loss could inhibit disease progression by reducing cytotoxic NO production by astrocytes and macrophages/microglia in the CNS.
520 $a My experiments provide the first evidence for the involvement of an arginine transporter in cancer metastasis and CNS pathology, and provide a foundation for future research in these areas.
590 $a School code: 0033.
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650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Health Sciences, Oncology. $3 1018566
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710 2 0 $a University of California, San Diego. $3 1018093
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