BIOSYNTHESIS OF PROLYL HYDROXYLASE
BIOSYNTHESIS OF PROLYL HYDROXYLASE
批准号:
3156116
负责人:
RICHARD A BERG
金额:
$16.86万
依托单位国家:
美国
项目类别:
财政年份:
1983
资助国家:
美国
项目状态:
已结题
起止时间:
1983-04-01 至 1988-11-30
关键词:
Ehlers Danlos syndrome atherosclerosis chick embryo collagen collagen disorder fibroblasts free radicals gel electrophoresis genetic transcription ion exchange chromatography lysosomes orphan disease /drug osteogenesis imperfecta procollagen pulmonary fibrosis /granuloma rheumatoid arthritis tissue /cell culture
中文摘要
本研究旨在描述溶酶体在调节胶原蛋白中的作用。
在成纤维细胞中产生。胶原蛋白的调节作用明确
与健康相关的影响,因为人类疾病的数量
与胶原蛋白代谢的变化有关。获得性障碍
如类风湿性关节炎、肺纤维化、肝硬变和
动脉粥样硬化,涉及胶原含量和类型的显著变化
在受影响的组织中。遗传性疾病,如Ehler Danlos
综合征和成骨不全表现出不同的方面
胶原蛋白调节方面的缺陷。基于来自几家公司的最新数据
实验室认为新合成的胶原蛋白的细胞内降解
在成纤维细胞中广泛存在,它可以部分地被抑制
溶酶体抑制物,溶酶体在胶原生物合成中的作用
被牵连了。溶酶体的一个作用已被证明涉及
在细胞内降解部分新合成的,
结构上有缺陷的胶原蛋白。溶酶体的第二个作用有待测试
以下是他们在翻译监管中的假设参与
胶原蛋白的合成和分泌。然而,溶酶体的作用是,
复杂的是至少存在一条非溶酶体途径
新合成的胶原蛋白的细胞内降解的基础水平。
本方案的第一个目的是使用培养的鸡腱
成纤维细胞以确定是否发现前胶原或前胶原片段
在溶酶体中。第二个目标是检查培养的成纤维细胞,这些细胞
分泌前胶原的能力受到抑制以确定是否降低
分泌也会导致翻译减少,如果这种减少
翻译是调节前胶原蛋白产生的结果,涉及
溶酶体。第三个目标是确定是否与溶酶体有关。
在摄取前胶原或前胶原延伸前肽中
无论是单独还是通过受体介导的过程。为了刻画出
培养成纤维细胞的进一步细胞内降解,第四个目标
就是检查降解的基础水平以确定氧气是否来源于
自由基和/或中性蛋白酶是造成这一重要原因的原因
非溶酶体途径。
英文摘要
This study aims at describing the role of lysosomes in regulating collagen
production in fibroblasts. The regulation of collagen has clear
health-related implications because of the number of human diseases that
are associated with a change in collagen metabolism. Acquired disorders
such as rheumatoid arthritis, pulmonary fibrosis, cirrhosis, and
atherosclerosis, involve significant changes in collagen content and type
in affected tissues. The genetic disorders such as the Ehlers Danlos
syndromes and Osteogenesis Imperfecta demonstrate various aspects of
deficiencies in collagen regulation. Based on recent data from several
laboratories that intracellular degradation of newly synthesized collagen
is widespread in fibroblasts and that it can in part be inhibited by
lysosomal inhibitors, a role for lysosomes in collagen biosynthesis has
been implicated. One role of lysosomes has been shown to involve the
degradation, intracellularly, of a portion of newly synthesized,
structurally defective, collagen. A second role for lysosomes to be tested
here is their hypothesized involvement in the translational regulation of
collagen synthesis and its secretion. The role of lysosomes is, however,
complicated by the presence of at least one non-lysosomal pathway for the
basal levels of intracellular degradation of newly synthesized collagen.
The first aim of the present proposal is to use cultured chick tendon
fibroblasts to determine if procollagen or procollagen fragments are found
in lysosomes. The second aim is to examine cultured fibroblasts which are
inhibited in theri ability to secrete procollagen to determine if decreased
secretion also results in decreased translation, and if this decreased
translation is a result of regulation of procollagen production involving
lysosomes. The third aim is to determine whether lysosomes may be involved
in the uptake of either procollagen or procollagen extension propeptides
either alone or by a receptor-mediated process. In order to characterize
further intracellular degradation in cultured fibroblasts, the fourth aim
is to examine the basal level of degradation to determine if oxygen-derived
free radicals and/or neutral proteases are responsible for this important
non-lysosomal pathway.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Injectable Delivery of Bone Growth Factor, HomoSer3-AIII
-
批准号:6992200
-
项目类别:
-
资助金额:$10.0万
-
财政年份:2005
-
负责人:RICHARD A BERG
-
依托单位:
BIOSYNTHESIS OF PROLYL HYDROXYLASE
-
批准号:3156112
-
项目类别:
-
资助金额:$18.41万
-
财政年份:1983
-
负责人:RICHARD A BERG
-
依托单位:
REGULATION OF PROLYL HYDROXYLASE
-
批准号:3156117
-
项目类别:
-
资助金额:$20.36万
-
财政年份:1983
-
负责人:RICHARD A BERG
-
依托单位:
BIOSYNTHESIS OF PROLYL HYDROXYLASE
-
批准号:3156115
-
项目类别:
-
资助金额:$18.52万
-
财政年份:1983
-
负责人:RICHARD A BERG
-
依托单位:
REGULATION OF PROLYL HYDROXYLASE
-
批准号:3156114
-
项目类别:
-
资助金额:$19.64万
-
财政年份:1983
-
负责人:RICHARD A BERG
-
依托单位:
海外基金