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PORPHYRIN INDUCED CA2+ RELEASE FROM SR

卟啉诱导 SR 释放 CA2

基本信息

批准号：
3439021
负责人：
JONATHAN J ABRAMSON
金额：
$ 10.64万
依托单位：
PORTLAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-04-01 至 1994-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3439021
关键词：
calcium channel chlorophyll cytochrome P450 electron transport hemoglobin hormone regulation /control mechanism laboratory rabbit muscle contraction myoglobin oxidation reduction reaction oxygen transport porphyrins ryanodine sarcoplasmic reticulum vitamin B12 coenzyme

项目摘要

Porphyrins are prosthetic groups for a large number of biological molecules which carry out diverse roles in nature. When coordinated to a central metal ion, porphyrins perform such functions as oxygen transport and storage (myoglobin and hemoglobin), electron and energy transfer (cytochromes and chlorophylls), and biocatalysis (coenzyme B12, cytochrome P-450). We have recently shown that low concentration of the porphyrin, meso-Tetra(4-N-methylpyridyl) porphine tetraiodide is a very potent stimulator of Ca2+ release from skeletal muscle sarcoplasmic reticulum (SR) vesicles. Experiments carried out using known inhibitors and stimulators of the Ca2+ release channel from sarcoplasmic reticulum indicate that this porphyrin is interacting with the Ca2+ release system from the SR. The main objective of this proposal are: (1) by testing various related porphyrins, determine whether of not there is a correlation between the effectiveness of stimulating Ca2+ release and the redox potential of the porphyrin. If a good correlation exists, (2) to estimate the redox potential of the receptor site at which the porphyrin interacts. (3) to determine directly how various porphyrins effect the gating characteristics of the Ca2+ release channel (a) following fusion of SR vesicles to an artificial membrane and (b) following incorporation of the isolated Ca2+ release protein from skeletal muscle sarcoplasmic reticulum. (4) To determine whether of not the " foot structure " which connects the T- tubule and the terminal end of the SR contains an endogenous porphyrin which is coupled t other Ca2+ release machinery via a redox reaction. In spite of recent advances in identifying a protein component involved in the Ca2+ release machinery, the molecular mechanism underlying excitation- contraction coupling remains unknown. As a result of this project, the interaction between porphyrins and the E-C coupling machinery in skeletal muscle will be described. If, as previously proposed, sulfhydryl oxidation and reduction is a key step in E-C coupling, this study should yield critical information regarding the gating and molecular interaction underlying this key step in skeletal muscle contraction.

卟啉是大量生物分子的修饰基。在自然界中扮演着不同的角色。当协调到中心时金属离子，卟啉具有氧运输和储存(肌红蛋白和血红蛋白)、电子和能量转移和生物催化(辅酶B12、细胞色素 P-450)。我们最近已经证明，低浓度的卟啉， Meso-四(4-N-甲基吡啶)四碘卟啉是一种非常有效的骨骼肌肌浆网钙离子释放的刺激物水泡。使用已知的抑制剂和刺激剂进行的实验肌浆网钙释放通道的变化表明这是卟啉与肌浆网钙离子释放系统相互作用。本方案的主要目标是：(1)通过测试各种相关的卟啉，确定之间是否存在相关性刺激细胞内钙释放和氧化还原电位的作用卟啉。如果存在良好的相关性，(2)估计氧化还原与卟啉相互作用的受体位置的电势。(3)至直接确定不同的卟啉如何影响门控特性 SR囊泡与An融合后钙释放通道(A)的变化人工膜和(B)掺入分离的钙离子后从骨骼肌肌浆网释放蛋白质。(4)至确定连接T-T的“脚结构”是否小管和SR的末端含有内源性的卟啉它通过氧化还原反应与其他钙释放机构相连。在……里面尽管最近在鉴定一种蛋白质成分方面取得了进展，这种蛋白质成分参与了钙离子释放机制，激发的分子机制- 收缩耦合仍然未知。作为这个项目的结果，卟啉与骨骼中E-C偶联机制的相互作用肌肉将被描述。如果像之前提议的那样，巯基氧化而还原是E-C耦合的关键一步，这项研究应该会产生关于门控和分子相互作用的关键信息在骨骼肌收缩的这一关键步骤下。