Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo
Abstract We previously reported that ibandronate (IBAN) could improve endothelial function in spontaneously hypertensive rats. However, the mechanism by which IBAN improves endothelial function is unclear. The IBAN-induced autophagic process in vitro experiments were determined by detection of LC3,...
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| Format: | Article |
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Nature Publishing Group
2022-04-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-00995-6 |
| _version_ | 1811291013797380096 |
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| author | Jie Han Jian Yang Qiqi Wang Xiang Yin Zewei Sun Chaoyang Huang Guoping Chen Liangrong Zheng Dongmei Jiang |
| author_facet | Jie Han Jian Yang Qiqi Wang Xiang Yin Zewei Sun Chaoyang Huang Guoping Chen Liangrong Zheng Dongmei Jiang |
| author_sort | Jie Han |
| collection | DOAJ |
| description | Abstract We previously reported that ibandronate (IBAN) could improve endothelial function in spontaneously hypertensive rats. However, the mechanism by which IBAN improves endothelial function is unclear. The IBAN-induced autophagic process in vitro experiments were determined by detection of LC3, Beclin1, and P62 protein levels via western blotting. The autophagy flux was detected by confocal microscopy and transmission electron microscopy. For in vivo experiments, spontaneously hypertensive rats were orally administered with IBAN. Utilizing angiotensin II (Ang II) to stimulate the human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) as a model of endothelial cell injury in hypertension, we found that IBAN promoted autophagy and protected cell viability in Ang II-treated-endothelial cells while these effects could be reversed by autophagy inhibitor. In terms of mechanism, IBAN treatment decreased the levels of Rac1 and mammalian target of rapamycin (mTOR) pathway. Activating either Rac1 or mTOR could reverse IBAN-induced autophagy. Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy by downregulating Rac1-mTOR. Taken together, our results firstly revealed that IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus alleviates Ang II-induced injury in endothelial cells. |
| first_indexed | 2024-04-13T04:23:05Z |
| format | Article |
| id | doaj.art-6740cec829ef439a85d9c6423f621ffc |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-13T04:23:05Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-6740cec829ef439a85d9c6423f621ffc2022-12-22T03:02:39ZengNature Publishing GroupCell Death Discovery2058-77162022-04-01811910.1038/s41420-022-00995-6Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivoJie Han0Jian Yang1Qiqi Wang2Xiang Yin3Zewei Sun4Chaoyang Huang5Guoping Chen6Liangrong Zheng7Dongmei Jiang8Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Endocrinology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAbstract We previously reported that ibandronate (IBAN) could improve endothelial function in spontaneously hypertensive rats. However, the mechanism by which IBAN improves endothelial function is unclear. The IBAN-induced autophagic process in vitro experiments were determined by detection of LC3, Beclin1, and P62 protein levels via western blotting. The autophagy flux was detected by confocal microscopy and transmission electron microscopy. For in vivo experiments, spontaneously hypertensive rats were orally administered with IBAN. Utilizing angiotensin II (Ang II) to stimulate the human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) as a model of endothelial cell injury in hypertension, we found that IBAN promoted autophagy and protected cell viability in Ang II-treated-endothelial cells while these effects could be reversed by autophagy inhibitor. In terms of mechanism, IBAN treatment decreased the levels of Rac1 and mammalian target of rapamycin (mTOR) pathway. Activating either Rac1 or mTOR could reverse IBAN-induced autophagy. Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy by downregulating Rac1-mTOR. Taken together, our results firstly revealed that IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus alleviates Ang II-induced injury in endothelial cells.https://doi.org/10.1038/s41420-022-00995-6 |
| spellingShingle | Jie Han Jian Yang Qiqi Wang Xiang Yin Zewei Sun Chaoyang Huang Guoping Chen Liangrong Zheng Dongmei Jiang Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo Cell Death Discovery |
| title | Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo |
| title_full | Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo |
| title_fullStr | Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo |
| title_full_unstemmed | Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo |
| title_short | Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo |
| title_sort | ibandronate promotes autophagy by inhibiting rac1 mtor signaling pathway in vitro and in vivo |
| url | https://doi.org/10.1038/s41420-022-00995-6 |
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