A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi
In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking a...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sciendo
2017-12-01
|
| Series: | Acta Pharmaceutica |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/acph-2017-0032 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832570316924125184 |
|---|---|
| author | Zhou Jie-Bin Sun Ying-Ying Zheng Ying-Lin Yu Chu-Qin Lin Hua-Qing Pang Ji-Yan |
| author_facet | Zhou Jie-Bin Sun Ying-Ying Zheng Ying-Lin Yu Chu-Qin Lin Hua-Qing Pang Ji-Yan |
| author_sort | Zhou Jie-Bin |
| collection | DOAJ |
| description | In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information about xyloketal A as a SOCE inhibitor for further evaluation. |
| format | Article |
| id | doaj-art-a4196fc5ffc245d6bdde7b5ff72c49c2 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2017-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-a4196fc5ffc245d6bdde7b5ff72c49c22025-02-02T15:49:11ZengSciendoActa Pharmaceutica1846-95582017-12-0167455756710.1515/acph-2017-0032acph-2017-0032A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungiZhou Jie-Bin0Sun Ying-Ying1Zheng Ying-Lin2Yu Chu-Qin3Lin Hua-Qing4Pang Ji-Yan5School of Chemistry Sun Yat-Sen University, Guangzhou 510275, P. R. ChinaDepartment of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms GuangDong Pharmaceutical University, Guangzhou 510006, P. R. ChinaSchool of Chemistry Sun Yat-Sen University, Guangzhou 510275, P. R. ChinaDepartment of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms GuangDong Pharmaceutical University, Guangzhou 510006, P. R. ChinaDepartment of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms GuangDong Pharmaceutical University, Guangzhou 510006, P. R. ChinaSchool of Chemistry Sun Yat-Sen University, Guangzhou 510275, P. R. ChinaIn this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information about xyloketal A as a SOCE inhibitor for further evaluation.https://doi.org/10.1515/acph-2017-0032xyloketal astore-operated calcium entrymolecular dockingil-8parallel artificial membrane permeability assay |
| spellingShingle | Zhou Jie-Bin Sun Ying-Ying Zheng Ying-Lin Yu Chu-Qin Lin Hua-Qing Pang Ji-Yan A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi Acta Pharmaceutica xyloketal a store-operated calcium entry molecular docking il-8 parallel artificial membrane permeability assay |
| title | A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi |
| title_full | A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi |
| title_fullStr | A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi |
| title_full_unstemmed | A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi |
| title_short | A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi |
| title_sort | study on blocking store operated ca2 entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi |
| topic | xyloketal a store-operated calcium entry molecular docking il-8 parallel artificial membrane permeability assay |
| url | https://doi.org/10.1515/acph-2017-0032 |
| work_keys_str_mv | AT zhoujiebin astudyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT sunyingying astudyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT zhengyinglin astudyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT yuchuqin astudyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT linhuaqing astudyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT pangjiyan astudyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT zhoujiebin studyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT sunyingying studyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT zhengyinglin studyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT yuchuqin studyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT linhuaqing studyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi AT pangjiyan studyonblockingstoreoperatedca2entryinpulmonaryarterialsmoothmusclecellswithxyloketalsfrommarinefungi |