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Title: Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8

Abstract

Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern. A Trp-Ala–Asp (WAD)-containing octapeptide, MTWADAEK, was thereafter synthesized and analyzed in functional assays. In the case of specific integrin antagonists as positive controls, the anti-angiogenic effects of CVX on HCASMCs were investigated by series of functional analyses. CVX showed to exhibit multiple inhibitory activities toward HCASMCs proliferation, adhesion and invasion with a dose- and integrin αvβ3-dependent fashion. However, the WAD-octapeptide exerting a minor potency could also work as an active peptidomimetic. In addition, flow cytometric analysis demonstrated both the intact CVX and synthetic peptide can specifically interact with integrin-αv on HCASMCs and CVX was shown to have a down-regulatory effect on the gene expression of CXC-chemokines, such as growth-related oncogene and interleukin-8. According to nuclear factor-κB (NF-κB) p65 translocation assay and Western blotting analysis, themore » NF-κB activation was not involved in the signaling events of CVX-induced gene expression. In conclusion, CVX may act as a disintegrin-like protein via the interactions of WAD-motif in CVX-β with integrin-αv on HCASMCs and it also is a gene suppressor with the ability to diminish the expression of two CXC-chemokines in a NF-κB-independent manner. Indeed, more extensive investigations are needed and might create a new avenue for the development of a novel angiostatic agent. - Highlights: • The tetrameric convulxin (CVX) with WAD-motif could affect HCASMC multi-functions. • CVX significantly diminished cell proliferation, adhesion and invasion in HCASMCs. • The WAD-motif/integrin-αv interaction was involved in its suppressive mechanism. • CVX impaired the gene expression of GRO and IL-8 with a NF-κB independent manner.« less

Authors:
;  [1];  [1];  [2]
  1. Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City, Taiwan (China)
  2. (China)
Publication Date:
OSTI Identifier:
22649835
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 352; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGGLOMERATION; ALBUMINS; CATTLE; CELL PROLIFERATION; COMPARATIVE EVALUATIONS; CORONARIES; ELECTROPHORESIS; ERRORS; FIBROBLASTS; FLUORESCENCE; FUNCTIONAL ANALYSIS; INHIBITION; INTERACTIONS; ISOTHIOCYANATES; LECTINS; LYMPHOKINES; MUSCLES; ONCOGENES; PEPTIDES; PLANT GROWTH; TRANSLOCATION

Citation Formats

Shih, Chun-Ho, Chiang, Tin-Bin, Wang, Wen-Jeng, E-mail: wjwang@mail.cgust.edu.tw, and Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan. Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.02.008.
Shih, Chun-Ho, Chiang, Tin-Bin, Wang, Wen-Jeng, E-mail: wjwang@mail.cgust.edu.tw, & Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan. Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8. United States. doi:10.1016/J.YEXCR.2017.02.008.
Shih, Chun-Ho, Chiang, Tin-Bin, Wang, Wen-Jeng, E-mail: wjwang@mail.cgust.edu.tw, and Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan. Wed . "Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8". United States. doi:10.1016/J.YEXCR.2017.02.008.
@article{osti_22649835,
title = {Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8},
author = {Shih, Chun-Ho and Chiang, Tin-Bin and Wang, Wen-Jeng, E-mail: wjwang@mail.cgust.edu.tw and Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan},
abstractNote = {Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern. A Trp-Ala–Asp (WAD)-containing octapeptide, MTWADAEK, was thereafter synthesized and analyzed in functional assays. In the case of specific integrin antagonists as positive controls, the anti-angiogenic effects of CVX on HCASMCs were investigated by series of functional analyses. CVX showed to exhibit multiple inhibitory activities toward HCASMCs proliferation, adhesion and invasion with a dose- and integrin αvβ3-dependent fashion. However, the WAD-octapeptide exerting a minor potency could also work as an active peptidomimetic. In addition, flow cytometric analysis demonstrated both the intact CVX and synthetic peptide can specifically interact with integrin-αv on HCASMCs and CVX was shown to have a down-regulatory effect on the gene expression of CXC-chemokines, such as growth-related oncogene and interleukin-8. According to nuclear factor-κB (NF-κB) p65 translocation assay and Western blotting analysis, the NF-κB activation was not involved in the signaling events of CVX-induced gene expression. In conclusion, CVX may act as a disintegrin-like protein via the interactions of WAD-motif in CVX-β with integrin-αv on HCASMCs and it also is a gene suppressor with the ability to diminish the expression of two CXC-chemokines in a NF-κB-independent manner. Indeed, more extensive investigations are needed and might create a new avenue for the development of a novel angiostatic agent. - Highlights: • The tetrameric convulxin (CVX) with WAD-motif could affect HCASMC multi-functions. • CVX significantly diminished cell proliferation, adhesion and invasion in HCASMCs. • The WAD-motif/integrin-αv interaction was involved in its suppressive mechanism. • CVX impaired the gene expression of GRO and IL-8 with a NF-κB independent manner.},
doi = {10.1016/J.YEXCR.2017.02.008},
journal = {Experimental Cell Research},
number = 2,
volume = 352,
place = {United States},
year = {Wed Mar 15 00:00:00 EDT 2017},
month = {Wed Mar 15 00:00:00 EDT 2017}
}