Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1
Vasohibin-1 (VASH1) is isolated as an endothelial cell (EC)-produced angiogenesis inhibitor. We questioned whether VASH1 plays any role besides angiogenesis inhibition, knocked-down or overexpressed VASH1 in ECs, and examined the changes of EC property. Knock-down of VASH1 induced premature senescen...
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Public Library of Science
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466306/ |
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pubmed-34663062012-10-10 Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 Miyashita, Hiroki Watanabe, Tatsuaki Hayashi, Hideki Suzuki, Yasuhiro Nakamura, Takanobu Ito, Soichi Ono, Manabu Hoshikawa, Yasushi Okada, Yoshinori Kondo, Takashi Sato, Yasufumi Research Article Vasohibin-1 (VASH1) is isolated as an endothelial cell (EC)-produced angiogenesis inhibitor. We questioned whether VASH1 plays any role besides angiogenesis inhibition, knocked-down or overexpressed VASH1 in ECs, and examined the changes of EC property. Knock-down of VASH1 induced premature senescence of ECs, and those ECs were easily killed by cellular stresses. In contrast, overexpression of VASH1 made ECs resistant to premature senescence and cell death caused by cellular stresses. The synthesis of VASH1 was regulated by HuR-mediated post-transcriptional regulation. We sought to define the underlying mechanism. VASH1 increased the expression of (superoxide dismutase 2) SOD2, an enzyme known to quench reactive oxygen species (ROS). Simultaneously, VASH1 augmented the synthesis of sirtuin 1 (SIRT1), an anti-aging protein, which improved stress tolerance. Paraquat generates ROS and causes organ damage when administered in vivo. More VASH1 (+/−) mice died due to acute lung injury caused by paraquat. Intratracheal administration of an adenovirus vector encoding human VASH1 augmented SOD2 and SIRT1 expression in the lungs and prevented acute lung injury caused by paraquat. Thus, VASH1 is a critical factor that improves the stress tolerance of ECs via the induction of SOD2 and SIRT1. Public Library of Science 2012-10-08 /pmc/articles/PMC3466306/ /pubmed/23056314 http://dx.doi.org/10.1371/journal.pone.0046459 Text en © 2012 Miyashita et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Miyashita, Hiroki Watanabe, Tatsuaki Hayashi, Hideki Suzuki, Yasuhiro Nakamura, Takanobu Ito, Soichi Ono, Manabu Hoshikawa, Yasushi Okada, Yoshinori Kondo, Takashi Sato, Yasufumi |
| spellingShingle |
Miyashita, Hiroki Watanabe, Tatsuaki Hayashi, Hideki Suzuki, Yasuhiro Nakamura, Takanobu Ito, Soichi Ono, Manabu Hoshikawa, Yasushi Okada, Yoshinori Kondo, Takashi Sato, Yasufumi Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 |
| author_facet |
Miyashita, Hiroki Watanabe, Tatsuaki Hayashi, Hideki Suzuki, Yasuhiro Nakamura, Takanobu Ito, Soichi Ono, Manabu Hoshikawa, Yasushi Okada, Yoshinori Kondo, Takashi Sato, Yasufumi |
| author_sort |
Miyashita, Hiroki |
| title |
Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 |
| title_short |
Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 |
| title_full |
Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 |
| title_fullStr |
Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 |
| title_full_unstemmed |
Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 |
| title_sort |
angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of sod2 and sirt1 |
| description |
Vasohibin-1 (VASH1) is isolated as an endothelial cell (EC)-produced angiogenesis inhibitor. We questioned whether VASH1 plays any role besides angiogenesis inhibition, knocked-down or overexpressed VASH1 in ECs, and examined the changes of EC property. Knock-down of VASH1 induced premature senescence of ECs, and those ECs were easily killed by cellular stresses. In contrast, overexpression of VASH1 made ECs resistant to premature senescence and cell death caused by cellular stresses. The synthesis of VASH1 was regulated by HuR-mediated post-transcriptional regulation. We sought to define the underlying mechanism. VASH1 increased the expression of (superoxide dismutase 2) SOD2, an enzyme known to quench reactive oxygen species (ROS). Simultaneously, VASH1 augmented the synthesis of sirtuin 1 (SIRT1), an anti-aging protein, which improved stress tolerance. Paraquat generates ROS and causes organ damage when administered in vivo. More VASH1 (+/−) mice died due to acute lung injury caused by paraquat. Intratracheal administration of an adenovirus vector encoding human VASH1 augmented SOD2 and SIRT1 expression in the lungs and prevented acute lung injury caused by paraquat. Thus, VASH1 is a critical factor that improves the stress tolerance of ECs via the induction of SOD2 and SIRT1. |
| publisher |
Public Library of Science |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466306/ |
| _version_ |
1611914427925266432 |