A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi-Reference-Cited by-同舟云学术

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

Published:2017-12-20 Issue:4 Volume:67 Page:557-567
ISSN:1846-9558
Container-title:Acta Pharmaceutica
language:en
Short-container-title:

Author:

Zhou Jie-Bin¹,Sun Ying-Ying²,Zheng Ying-Lin¹,Yu Chu-Qin²,Lin Hua-Qing²,Pang Ji-Yan¹

Affiliation:

1. School of Chemistry Sun Yat-Sen University, Guangzhou 510275, P. R. China

2. Department of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms GuangDong Pharmaceutical University, Guangzhou 510006, P. R. China

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Pharmaceutical Science,Pharmacology,General Medicine

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