FUNCTION OF GAMMA GLUTAMYL LEUKOTRIENASE
伽玛谷氨酰白三烯酶的功能
基本信息
- 批准号:6635474
- 负责人:
- 金额:$ 33.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1996
- 资助国家:美国
- 起止时间:1996-03-01 至 2006-02-28
- 项目状态:已结题
- 来源:
- 关键词:aminoacid metabolism asthma cell membrane cell migration cysteine electrospray ionization mass spectrometry enzyme mechanism enzyme structure epithelium exopeptidase fatty acid metabolism glutamyltransferase glutathione glycosylation growth /development immunocytochemistry inflammation juvenile animal laboratory mouse leukotrienes liquid chromatography mass spectrometry neutrophil protein localization vascular endothelium
项目摘要
DESCRIPTION: Gamma-Glutamyl transpeptidase (GGT) and gamma-glutamyl
leukotrienase (GGL), a related enzyme identified in the applicant's laboratory,
belong to a small gene family that cleaves glutathione (GSH) and GSH
conjugates. Although many of the physiologic functions of GGT are known, those
of GGL not as well characterized. The applicant's laboratory has cloned GGL,
raised antibodies to it, and developed mice with a targeted GGL mutation
(GGLtm1). Preliminary data indicate that GGLtm1 is a null mutation. For the
purposes of the study, mice have also been generated with a targeted GGT null
mutation and mice carrying targeted cis mutations in both genes.
GGL and GGT convert cysteinyl leukotriene (LT) C4 to LTD4, the most potent
cysteinyl LT. Dipeptidases including membrane bound dipeptidase (MBD) convert
LTD4 to LTE4, a very weak LT. Cysteinyl LTs mediate vascular permeability,
smooth muscle contraction, eosinophil function and mucus formation. The
applicant proposes to study the structure, cellular localization, and tissue
distribution of GGL, assess its function by using GGL-, GGT-, and
GGL/GGT-deficient mice, and test hypotheses about the role of these genes in
inflammation and asthma. MBD-deficient mice with a partial block in LTD4 to
LTE4 conversion have also been developed. Plans are described to treat them
with a dipeptidase inhibitor in order to assess LTE4' and LTD4 role in
inflammation and asthma. Specific Aims of this proposal include:
1. Demonstration that GGLtml is a null mutation and to examine its physiologic
consequences.
2. Testing of the hypothesis that GGL consists of a light chain and a
glycosylated heavy chain and is expressed on the surface of endothelial cells.
3. Testing of the hypotheses that LTD4 is the principal cysteinyl LT mediator
of inflammation and a significant contributor to neutrophil migration.
4. Testing of the hypothesis that LTD4 is the principal cysteinyl LT mediator
of bronchial asthma.
性状:γ-谷氨酰转肽酶(GGT)和γ-谷氨酰
白三烯酶(GGL),申请人实验室鉴定的相关酶,
属于一个小的基因家族,切割谷胱甘肽(GSH)和GSH
结合物。虽然GGT的许多生理功能是已知的,但这些功能可能是不确定的。
GGL的特征并不明显。申请人的实验室克隆了GGL,
针对它产生了抗体,并培育出具有靶向GGL突变的小鼠,
(GGLtm1)。初步数据表明GGLtm 1是无效突变。为
为了研究的目的,还产生了具有靶向GGT空的小鼠。
突变和在两个基因中携带靶向顺式突变的小鼠。
GGL和GGT将半胱氨酰白三烯(LT)C4转化为LTD 4,
包括膜结合二肽酶(MBD)的半胱氨酰LT.二肽酶转化
LTD 4到LTE 4,一种非常弱的LT。半胱氨酰LT介导血管通透性,
平滑肌收缩、嗜酸性粒细胞功能和粘液形成。的
申请人提出研究结构、细胞定位和组织
GGL的分布,通过使用GGL-、GGT-和
GGL/GGT缺陷小鼠,并测试关于这些基因在
炎症和哮喘。在LTD 4中部分阻断的MBD缺陷小鼠,
LTE 4转换也已经开发。计划被描述为治疗他们
与二肽酶抑制剂,以评估LTE 4 '和LTD 4在
炎症和哮喘。该提案的具体目标包括:
1.证明GGLtml是无效突变,并检查其生理活性。
后果
2. GGL由轻链和轻链组成的假设的检验
糖基化重链,并在内皮细胞表面表达。
3. LTD 4是主要半胱氨酰LT介质的假设的检验
炎症的发生和中性粒细胞迁移的重要贡献者。
4. LTD 4是主要半胱氨酰LT介导剂的假设的检验
支气管哮喘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael Lieberman其他文献
Michael Lieberman的其他文献
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{{ truncateString('Michael Lieberman', 18)}}的其他基金
AS-GSH CONJUGATION LIMITS AS AVAILABILITY & TOXICITY
AS-GSH 结合限制了可用性
- 批准号:
6751962 - 财政年份:2000
- 资助金额:
$ 33.86万 - 项目类别:
AS-GSH CONJUGATION LIMITS AS AVAILABILITY & TOXICITY
AS-GSH 结合限制了可用性
- 批准号:
6518175 - 财政年份:2000
- 资助金额:
$ 33.86万 - 项目类别:
AS-GSH CONJUGATION LIMITS AS AVAILABILITY & TOXICITY
AS-GSH 结合限制了可用性
- 批准号:
6087177 - 财政年份:2000
- 资助金额:
$ 33.86万 - 项目类别:
AS-GSH CONJUGATION LIMITS AS AVAILABILITY & TOXICITY
AS-GSH 结合限制了可用性
- 批准号:
6635509 - 财政年份:2000
- 资助金额:
$ 33.86万 - 项目类别:
AS-GSH CONJUGATION LIMITS AS AVAILABILITY & TOXICITY
AS-GSH 结合限制了可用性
- 批准号:
6382356 - 财政年份:2000
- 资助金额:
$ 33.86万 - 项目类别:
RESPONSE TO INJURY IN GAMMAGLUTAMYL CYCLE DEFICIENT MICE
丙谷氨酰循环缺陷小鼠对损伤的反应
- 批准号:
6624932 - 财政年份:1996
- 资助金额:
$ 33.86万 - 项目类别:
RESPONSE TO INJURY IN GAMMAGLUTAMYL CYCLE DEFICIENT MICE
丙谷氨酰循环缺陷小鼠对损伤的反应
- 批准号:
6041314 - 财政年份:1996
- 资助金额:
$ 33.86万 - 项目类别:
METABOLISM IN GAMMA-GLUTAMY1 TRANSPEPTIDASE DEFICT MICE
GAMMA-GLUTAMY1 转肽酶缺陷小鼠的代谢
- 批准号:
2882839 - 财政年份:1996
- 资助金额:
$ 33.86万 - 项目类别:
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