| RRC ID |
51862
|
| 著者 |
Hazawa M, Yasuda T, Saotome-Nakamura A, Tomiyama K, Obara C, Goto T, Tajima K.
|
| タイトル |
Intra- and extracellular plasminogen activator inhibitor-1 regulate effect of vitronectin against radiation-induced endothelial cell death.
|
| ジャーナル |
Vascul Pharmacol
|
| Abstract |
Plasminogen activator inhibitor-1 (PAI-1) is induced by radiation resulting in endothelial cell impairment, potentially leading to multiple organ failure. Vitronectin (VN) is a 75-kDa glycoprotein (VN75) cleaved into two forms (VN75 or VN65/10) by furin, which is regulated by intracellular PAI-1. VN protects against radiation-induced endothelial cell death, but the mechanisms involved in VN processing and its interactions with intra- and extracellular PAI-1 remain unclear. We examined these processes in cells in vitro using recombinant proteins or overexpression of VN and PAI-1 genes, including furin-susceptible (T381) and furin-resistant VN (A381). VN processing was analyzed using a mutant PAI-1 with relatively weaker binding to VN. VN function was evaluated by survival of radiation-damaged endothelial cells. Wild-type, but not mutant PAI-1 inhibited furin-dependent VN processing. Gene transfer revealed that furin-susceptible VN was processed more than the furin-resistant form, but processing of both was inhibited by PAI-1 overexpression. Intracellular PAI-1 formed a complex with VN75 (T381) in cells and media, and the VN75 form was secreted preferentially. Only VN75 protected against radiation-induced endothelial cell death, in which its effect was abolished by wild-type but not mutant PAI-1. These findings indicate that intracellular PAI-1 inhibits VN processing and protects against radiation-induced endothelial cell death.
|
| 巻・号 |
87
|
| ページ |
150-158
|
| 公開日 |
2016-12-1
|
| DOI |
10.1016/j.vph.2016.09.006
|
| PII |
S1537-1891(15)30122-1
|
| PMID |
27650166
|
| MeSH |
Cell Death / radiation effects
Endothelial Cells / metabolism*
Endothelial Cells / radiation effects
Furin / metabolism
HEK293 Cells
Hep G2 Cells
Humans
Mutation
Plasminogen Activator Inhibitor 1 / genetics
Plasminogen Activator Inhibitor 1 / metabolism*
Radiation Injuries / genetics
Radiation Injuries / pathology
Radiation Injuries / prevention & control*
Vitronectin / genetics
Vitronectin / metabolism*
|
| IF |
3.607
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
