Open AccessProtective role of epigallocatechin‐3‐gallate in NADPH oxidase‐MMP2‐Spm‐Cer‐S1P signalling axis mediated ET‐1 induced pulmonary artery smooth muscle cell proliferation
Author(s) -
Sarkar Jaganmay,
Chakraborti Tapati,
Chowdhury Animesh,
Bhuyan Rajabrata,
Chakraborti Sajal
Publication year - 2019
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-018-00501-7
Subject(s) - nadph oxidase , sphingosine , sphingomyelin phosphodiesterase , sphingosine kinase , cell growth , chemistry , ceramide , sphingomyelin , rho associated protein kinase , microbiology and biotechnology , nox1 , sphingosine 1 phosphate , signal transduction , biochemistry , biology , reactive oxygen species , receptor , apoptosis , membrane
The signalling pathway involving MMP‐2 and sphingosine‐1‐phosphate (S1P) in endothelin‐1 (ET‐1) induced pulmonary artery smooth muscle cell (PASMC) proliferation is not clearly known. We, therefore, investigated the role of NADPH oxidase derived O 2 .‐ ‐mediated modulation of MMP2‐sphingomyeline‐ceramide‐S1P signalling axis in ET‐1 induced increase in proliferation of PASMCs. Additionally, protective role of the tea cathechin, epigallocatechin‐3‐gallate (EGCG), if any, in this scenario has also been explored. ET‐1 markedly increased NADPH oxidase and MMP‐2 activities and proliferation of bovine pulmonary artery smooth muscle cells (BPASMCs). ET‐1 also caused significant increase in sphingomyelinase (SMase) activity, ERK1/2 and sphingosine kinase (SPHK) phosphorylations, and S1P level in the cells. EGCG inhibited ET‐1 induced increase in SMase activity, ERK1/2 and SPHK phosphorylations, S1P level and the SMC proliferation. EGCG also attenuated ET‐1 induced activation of MMP‐2 by inhibiting NADPH oxidase activity upon inhibiting the association of the NADPH oxidase components, p47phox and p67phox in the cell membrane. Molecular docking study revealed a marked binding affinity of p47phox with the galloyl group of EGCG. Overall, our study suggest that ET‐1 induced proliferation of the PASMCs occurs via NADPH oxidase‐MMP2‐ Spm‐ Cer‐S1P signalling axis, and EGCG attenuates ET‐1 induced increase in proliferation of the cells by inhibiting NADPH oxidase activity.