1999 Fiscal Year Final Research Report Summary
Clinical Therapeutic Research of Calcium Sensitization
| Project/Area Number |
10470511
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Mie University |
|---|
Principal Investigator |
TANAKA Toshio Mie University, Faculty of Medicine, Professor, 医学部, 教授 (00135443)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUNODA Hiroshi Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (20314114)
NISHIMURA Yuhei Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (30303720)
NAKA Michiko Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (10093139)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | calcium sensitization / S100C / actin / Mg2+-ATPase / hypoxia / gene expression |
|---|
| Research Abstract |
Changes in cytosolic CaィイD12+ィエD1 concentration control a wide range of cellular responses. It is known that the relationship of cytosolic CaィイD12+ィエD1 concentration and the cellular response changes in various conditions, suggesting that calcium sensitization regulate the response. Intracellular CaィイD12+ィエD1-binding proteins are the key molecules to transduce CaィイD12+ィエD1 signaling via interactions with different types of target proteins. Recently, we purified S100C, a novel calcium binding protein, cloned and sequenced its cDNA. In this study, we found that S100C inhibited the actin-activated myosin MgィイD12+ィエD1-ATPase activity of smooth muscle in a dose-dependent manner. Furthermore, S100C was found to bind to actin in the presence of CaィイD12+ィエD1. The results suggest that S100C might play an important role in calcium sensitization through its CaィイD12+ィエD1-Adependent interaction with actin filaments. Moreover, we cloned and sequenced the S100C gene. Exposure to hypoxia results in elevation of cytosolic CaィイD12+ィエD1 concentration and vascular smooth muscle cells to hypoxic conditions in vitro, and detected the up-regulation of S100C mRNA. Reporter plasmids carrying the 5'-flanking region of the S100C gene connected to the luciferase structural gene were constructed and transfected. The luciferase activity of each plasmid in hypoxia was investigated. We found that the transcriptional induction of the S100C gene was regulated through the hypoxia response elements in the promoter region of S100C gene.
|
