Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes
Background/Aims: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and othe...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2016-02-01
|
| Series: | Kidney & Blood Pressure Research |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/443417 |
| _version_ | 1818159901711532032 |
|---|---|
| author | Weili Wang Juan Cai Sha Tang Ying Zhang Xuejing Gao Lijiao Xie Zhirong Mou Yuzhang Wu Li Wang Jingbo Zhang |
| author_facet | Weili Wang Juan Cai Sha Tang Ying Zhang Xuejing Gao Lijiao Xie Zhirong Mou Yuzhang Wu Li Wang Jingbo Zhang |
| author_sort | Weili Wang |
| collection | DOAJ |
| description | Background/Aims: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion. The present study evaluated the effect of SN in podocytes induced by Ang II. Methods: Podocytes were pretreated with graded concentrations (10-8 M ∼ 10-4 M) of SN and then stimulated with Ang II. The LC3B protein and the p47-phox membrane fraction were measured by Western blot. Autolysosomes were assessed by transmission electron microscopy. FACS was used to quantify the ROS produced by podocytes. The translocation of p47-phox to the membrane was investigated by immunofluorescence. Results: The 10-8 M ∼ 10-4 M of SN alone did not effect ROS generation or podocyte autophagy. The 10-8 M and 10-6 M SN attenuated Ang II-induced autophagy in podocytes. Furthermore, SN decreased the level of ROS generation in Ang II-induced podocytes via inhibition of NOX subunit p47-phox translocation to the membrane. Conclusion: The appropriate concentration of SN attenuated Ang II-induced podocyte autophagy through ROS generation, at least in part, by regulating NOX subunit p47-phox translocation to the membrane. |
| first_indexed | 2024-12-11T15:53:21Z |
| format | Article |
| id | doaj.art-7cd92db4cc9a4990a034be343650be06 |
| institution | Directory Open Access Journal |
| issn | 1420-4096 1423-0143 |
| language | English |
| last_indexed | 2024-12-11T15:53:21Z |
| publishDate | 2016-02-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Kidney & Blood Pressure Research |
| spelling | doaj.art-7cd92db4cc9a4990a034be343650be062022-12-22T00:59:31ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432016-02-0141215816710.1159/000443417443417Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in PodocytesWeili WangJuan CaiSha TangYing ZhangXuejing GaoLijiao XieZhirong MouYuzhang WuLi WangJingbo ZhangBackground/Aims: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion. The present study evaluated the effect of SN in podocytes induced by Ang II. Methods: Podocytes were pretreated with graded concentrations (10-8 M ∼ 10-4 M) of SN and then stimulated with Ang II. The LC3B protein and the p47-phox membrane fraction were measured by Western blot. Autolysosomes were assessed by transmission electron microscopy. FACS was used to quantify the ROS produced by podocytes. The translocation of p47-phox to the membrane was investigated by immunofluorescence. Results: The 10-8 M ∼ 10-4 M of SN alone did not effect ROS generation or podocyte autophagy. The 10-8 M and 10-6 M SN attenuated Ang II-induced autophagy in podocytes. Furthermore, SN decreased the level of ROS generation in Ang II-induced podocytes via inhibition of NOX subunit p47-phox translocation to the membrane. Conclusion: The appropriate concentration of SN attenuated Ang II-induced podocyte autophagy through ROS generation, at least in part, by regulating NOX subunit p47-phox translocation to the membrane.http://www.karger.com/Article/FullText/443417NADPH oxidasep47-phoxPodocyteAngiotensin IIAutophagySinomenine |
| spellingShingle | Weili Wang Juan Cai Sha Tang Ying Zhang Xuejing Gao Lijiao Xie Zhirong Mou Yuzhang Wu Li Wang Jingbo Zhang Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes Kidney & Blood Pressure Research NADPH oxidase p47-phox Podocyte Angiotensin II Autophagy Sinomenine |
| title | Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes |
| title_full | Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes |
| title_fullStr | Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes |
| title_full_unstemmed | Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes |
| title_short | Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes |
| title_sort | sinomenine attenuates angiotensin ii induced autophagy via inhibition of p47 phox translocation to the membrane and influences reactive oxygen species generation in podocytes |
| topic | NADPH oxidase p47-phox Podocyte Angiotensin II Autophagy Sinomenine |
| url | http://www.karger.com/Article/FullText/443417 |
| work_keys_str_mv | AT weiliwang sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT juancai sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT shatang sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT yingzhang sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT xuejinggao sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT lijiaoxie sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT zhirongmou sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT yuzhangwu sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT liwang sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes AT jingbozhang sinomenineattenuatesangiotensiniiinducedautophagyviainhibitionofp47phoxtranslocationtothemembraneandinfluencesreactiveoxygenspeciesgenerationinpodocytes |