The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction
博士 === 國防醫學院 === 生命科學研究所 === 100 === Increased endothelial permeability has been regarded as a key step contributing to hypoxia-associated vascular disorders, such as atherosclerosis and metastasis of tumors. To date, it is not known what strategy might be used to counter the effect of hypoxia on en...
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ndltd-TW-100NDMC01050072015-10-19T04:03:03Z http://ndltd.ncl.edu.tw/handle/87810060375664273520 The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction 亞硝酸鹽於缺氧誘發之內皮細胞屏障功能損傷的作用機制及生理功能研究 Lai, Yen-Chun 賴彥錞 博士 國防醫學院 生命科學研究所 100 Increased endothelial permeability has been regarded as a key step contributing to hypoxia-associated vascular disorders, such as atherosclerosis and metastasis of tumors. To date, it is not known what strategy might be used to counter the effect of hypoxia on endothelial permeability. This study investigated the role of nitrite in regulating vascular integrity under hypoxic conditions. We found denitrosylation and the resulting activation of caspase-3 to be critical for hypoxia-induced endothelial permeability. Treatment with nitrite results in renitrosylation and the inactivation of caspase-3, thus suppressing the barrier dysfunction of endothelia caused by hypoxia. This process required the conversion of nitrite to bioactive nitric oxide (NO) in a nitrite reductase-dependent manner. Using primary HUVECs as a model, we showed that in the presence of nitrite, the S-nitrosylated and inactivated form of caspase-3 was unable to cleave B-catenin, a key component in the VE-cadherin complex. Therefore, nitrite treatment led to the maintenance of VE-cadherin-mediated adherens junctions under hypoxic conditions. Furthermore, using an in vivo zebrafish model, nitrite was found to protect blood vessels from vascular leakage caused by hypoxia. Our findings reveal a molecular basis for the protective effect of nitrite in preventing hypoxia-induced endothelial barrier dysfunction and shed lights on the therapeutic potential of nitrite for the treatment of hypoxia-associated disorders. Meng, Tzu-Ching 孟子青 2011 學位論文 ; thesis 84 en_US |
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博士 === 國防醫學院 === 生命科學研究所 === 100 === Increased endothelial permeability has been regarded as a key step contributing to hypoxia-associated vascular disorders, such as atherosclerosis and metastasis of tumors. To date, it is not known what strategy might be used to counter the effect of hypoxia on endothelial permeability. This study investigated the role of nitrite in regulating vascular integrity under hypoxic conditions. We found denitrosylation and the resulting activation of caspase-3 to be critical for hypoxia-induced endothelial permeability. Treatment with nitrite results in renitrosylation and the inactivation of caspase-3, thus suppressing the barrier dysfunction of endothelia caused by hypoxia. This process required the conversion of nitrite to bioactive nitric oxide (NO) in a nitrite reductase-dependent manner. Using primary HUVECs as a model, we showed that in the presence of nitrite, the S-nitrosylated and inactivated form of caspase-3 was unable to cleave B-catenin, a key component in the VE-cadherin complex. Therefore, nitrite treatment led to the maintenance of VE-cadherin-mediated adherens junctions under hypoxic conditions. Furthermore, using an in vivo zebrafish model, nitrite was found to protect blood vessels from vascular leakage caused by hypoxia. Our findings reveal a molecular basis for the protective effect of nitrite in preventing hypoxia-induced endothelial barrier dysfunction and shed lights on the therapeutic potential of nitrite for the treatment of hypoxia-associated disorders.
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author2 |
Meng, Tzu-Ching |
author_facet |
Meng, Tzu-Ching Lai, Yen-Chun 賴彥錞 |
author |
Lai, Yen-Chun 賴彥錞 |
spellingShingle |
Lai, Yen-Chun 賴彥錞 The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction |
author_sort |
Lai, Yen-Chun |
title |
The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction |
title_short |
The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction |
title_full |
The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction |
title_fullStr |
The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction |
title_full_unstemmed |
The Mechanism And Function Of Nitrite On Hypoxia-induced Endothelial Barrier Dysfunction |
title_sort |
mechanism and function of nitrite on hypoxia-induced endothelial barrier dysfunction |
publishDate |
2011 |
url |
http://ndltd.ncl.edu.tw/handle/87810060375664273520 |
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