Protein disulfide isomerase externalization in endothelial cells follows classical and unconventional routes

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art_ARAUJO_Protein_disulfide_isomerase_externalization_in_endothelial_cells_follows_2017.PDF (1.03 MB)
Citações na Scopus
35
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
ZEIDLERA, Julianna D.
DIAS, Matheus H.
ARMELIN, Hugo A.
Citação
FREE RADICAL BIOLOGY AND MEDICINE, v.103, p.199-208, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Extracellular protein disulfide isomerase (PDIA1) pool mediates thrombosis and vascular remodeling, however its externalization mechanisms remain unclear. We performed systematic pharmacological screening of secretory pathways affecting extracellular PDIA1 in endothelial cells (EC). We identified cell-surface (csPDIA1) and secreted non-particulated PDIA1 pools in EC. Such Golgi bypass also occurred for secreted PDIA1 in EC at baseline or after PMA, thrombin or ATP stimulation. Inhibitors of Type I, II and III unconventional routes, secretory lysosomes and recycling endosomes, including syntaxin-12 deletion, did not impair EC PDIA1 externalization This suggests predominantly Golgi-independent unconventional secretory route(s), which were GRASP55-independent. Also, these data reinforce a vesicular-type traffic for PDIA1. We further showed that PDIA1 traffic is ATP-independent, while actin or tubulin cytoskeletal disruption markedly increased EC PDIA1 secretion. Clathrin inhibition enhanced extracellular soluble PDIA1, suggesting dynamic cycling. Externalized PDIA1 represents <2% of intracellular PDIA1. PDIA1 was robustly secreted by physiological levels of arterial laminar shear in EC and supported alpha 5 integrin thiol oxidation. Such results help clarify signaling and homeostatic mechanisms involved in multiple (patho)physiological extracellular PDIA1 functions.
Palavras-chave
Protein disulfide isomerase, Golgi bypass, Shear stress, Endothelial cell, Vascular smooth muscle
URI
https://observatorio.fm.usp.br/handle/OPI/19099
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Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/19