Golgi-independent routes support protein disulfide isomerase externalization in vascular smooth muscle cells

Autor(es)

Araujo, Thais L. S. ; Fernandes, Carolina G. ; Laurindo, Francisco R. M.

• Tipo de documento: Artigo Científico
• Fonte: REDOX BIOLOGY; v. 12, p. 1004-1010, AUG 2017.
• Citações Web of Science: 6

Resumo

Extracellular pools of intracellular molecular chaperones are increasingly evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and vascular remodeling, while PDI externalization routes remain elusive. In endothelial cells, vesicular-type PDI secretion involves classical and unconventional pathways, while in platelets PDI exocytosis involves actin cytoskeleton. However, little is known about pecPDI in vascular smooth muscle cells(VSMC). Here, we showed that VSMC display a robust cell-surface(cs) PDI pool, which binds to cs independently of electrostatic forces. However, contrarily to other cells, soluble secreted PDI pool was undetectable in VSMC. Calcium ionophore A23187 and TNF alpha enhanced VSMC csPDI. Furthermore, VSMC PDI externalization occurred via Golgi-bypass unconventional route, which was independent of cytoskeleton or lysosomes. Secreted PDI was absent in ex vivo wild-type mice aortas but markedly enhanced in PDI-overexpressing mice. Such characterization of VSMC pecPDI reinforces cell-type and context specific routes of PDI externalization. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/02372-0 - Mecanismos e efeitos redox da dissulfeto isomerase proteica EPI ou pericelular (epcPDI)
• Beneficiário: Thaís Larissa Araujo de Oliveira Silva
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/06210-2 - Envolvimento da via da GRASP na externalização da dissulfeto isomerase proteica-A1 e sua implicação na resposta de células endoteliais a shear stress
• Beneficiário: Thaís Larissa Araujo de Oliveira Silva
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado