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Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy

Genipin (GP) is commonly used to treat cardiovascular diseases; however, the protective action of GP against vascular hyperpermeability (VH) has not been reported. We previously reported that intrinsic apoptotic signaling (IAS) is involved in VH following hemorrhagic shock (HS). GP inhibits apoptosi...

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Autores principales: Shumin, Cai, Wei, Xu, Yunfeng, Li, Jiangshui, Liang, Youguang, Gao, Zhongqing, Chen, Tao, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943516/
https://www.ncbi.nlm.nih.gov/pubmed/29760950
http://dx.doi.org/10.1038/s41420-018-0057-2
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author Shumin, Cai
Wei, Xu
Yunfeng, Li
Jiangshui, Liang
Youguang, Gao
Zhongqing, Chen
Tao, Li
author_facet Shumin, Cai
Wei, Xu
Yunfeng, Li
Jiangshui, Liang
Youguang, Gao
Zhongqing, Chen
Tao, Li
author_sort Shumin, Cai
collection PubMed
description Genipin (GP) is commonly used to treat cardiovascular diseases; however, the protective action of GP against vascular hyperpermeability (VH) has not been reported. We previously reported that intrinsic apoptotic signaling (IAS) is involved in VH following hemorrhagic shock (HS). GP inhibits apoptosis, but the specific mechanism remains unclear. In the present study, we observed that GP protects against HS-induced VH in vitro and in vivo. We report that this protective effect is related to the inhibition of IAS by up-regulation of autophagy via sirtuin 3 (SIRT3). The endothelial cell hyperpermeability induced by HS was enhanced by GP; this was attenuated by 3-methyladenine (3MA), a specific inhibitor of autophagy, indicating the involvement of autophagy. Consistent with these results, we found that 3MA reversed the effects of GP on up-regulation of autophagy, and also diminished the protective effect of GP against IAS activation following HS. Furthermore, knockout of SIRT3 inhibited GP-induced autophagy, indicating the requirement of SIRT3 in the regulation of autophagy by GP. In rats, GP improved HS-induced VH, which was repressed by 3MA and 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP), a SIRT3 inhibitor. In conclusion, these findings suggest that autophagy plays a protective effect in VH following HS; the protective effect of autophagy is reinforced by GP, which protects against IAS and VH by up-regulating SIRT3.
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spelling pubmed-59435162018-05-14 Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy Shumin, Cai Wei, Xu Yunfeng, Li Jiangshui, Liang Youguang, Gao Zhongqing, Chen Tao, Li Cell Death Discov Article Genipin (GP) is commonly used to treat cardiovascular diseases; however, the protective action of GP against vascular hyperpermeability (VH) has not been reported. We previously reported that intrinsic apoptotic signaling (IAS) is involved in VH following hemorrhagic shock (HS). GP inhibits apoptosis, but the specific mechanism remains unclear. In the present study, we observed that GP protects against HS-induced VH in vitro and in vivo. We report that this protective effect is related to the inhibition of IAS by up-regulation of autophagy via sirtuin 3 (SIRT3). The endothelial cell hyperpermeability induced by HS was enhanced by GP; this was attenuated by 3-methyladenine (3MA), a specific inhibitor of autophagy, indicating the involvement of autophagy. Consistent with these results, we found that 3MA reversed the effects of GP on up-regulation of autophagy, and also diminished the protective effect of GP against IAS activation following HS. Furthermore, knockout of SIRT3 inhibited GP-induced autophagy, indicating the requirement of SIRT3 in the regulation of autophagy by GP. In rats, GP improved HS-induced VH, which was repressed by 3MA and 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP), a SIRT3 inhibitor. In conclusion, these findings suggest that autophagy plays a protective effect in VH following HS; the protective effect of autophagy is reinforced by GP, which protects against IAS and VH by up-regulating SIRT3. Nature Publishing Group UK 2018-05-09 /pmc/articles/PMC5943516/ /pubmed/29760950 http://dx.doi.org/10.1038/s41420-018-0057-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shumin, Cai
Wei, Xu
Yunfeng, Li
Jiangshui, Liang
Youguang, Gao
Zhongqing, Chen
Tao, Li
Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy
title Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy
title_full Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy
title_fullStr Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy
title_full_unstemmed Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy
title_short Genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of SIRT3/autophagy
title_sort genipin alleviates vascular hyperpermeability following hemorrhagic shock by up-regulation of sirt3/autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943516/
https://www.ncbi.nlm.nih.gov/pubmed/29760950
http://dx.doi.org/10.1038/s41420-018-0057-2
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