<abstract xmlns="http://www.w3.org/1999/xhtml"><p> 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.</p></abstract>

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.

A study on blocking store-operated Ca<sup>2+</sup> entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

A study on blocking store-operated Ca 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...

A study on blocking store-operated Ca²⁺ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

Publié en ligne: 11 janv. 2018

Pages: 557 - 567

Accepté: 22 juin 2017

DOI: https://doi.org/10.1515/acph-2017-0032

Mots clés
xyloketal A, store-operated calcium entry, molecular docking, IL-8, parallel artificial membrane permeability assay

© by Hua-Qing Lin

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

Publié en ligne: 11 janv. 2018

Pages: 557 - 567

Accepté: 22 juin 2017

DOI: https://doi.org/10.1515/acph-2017-0032

Mots clésxyloketal A, store-operated calcium entry, molecular docking, IL-8, parallel artificial membrane permeability assay

© by Hua-Qing Lin

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

A study on blocking store-operated Ca²⁺ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

Mots clés
xyloketal A, store-operated calcium entry, molecular docking, IL-8, parallel artificial membrane permeability assay