Protein Disulfide Isomerase and Nox: New Partners in Redox Signaling

Autor(es)

Trevelin, Silvia Cellone ^{[1, 2]} ; Lopes, Lucia Rossetti ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CURRENT PHARMACEUTICAL DESIGN; v. 21, n. 41, p. 5951-5963, 2015.
• Citações Web of Science: 17

Resumo

Reactive oxygen species (ROS) contribute to the pathogenesis of cardiovascular diseases, including hypertension, atherosclerosis, cardiac hypertrophy, heart failure and restenosis. Thiol proteins and thiol oxidoreductases are key players in cell signaling, and their altered expression and/or activity has been associated with a disrupture in cardiac and vascular homeostasis. Protein disulfide isomerase (PDI) is a thiol oxidoreductase member of the thioredoxin family that has multiple roles in cellular function. Originally discovered in the endoplasmic reticulum (ER), PDI is essential for protein folding. However, it can also be found in the cytosol and closely associated with the surface of platelets, smooth muscle cells, neutrophils and endothelial cells. On the cell surface, PDI is imperative for platelet aggregation and transnitrosation, which are related to thrombosis and control of vascular tone by nitric oxide, respectively. Furthermore, PDI signaling contributes to redox-dependent events such as smooth muscle cell migration induced by PDGF and TNF alpha-dependent angiogenesis. Studies from our group have shown that intracellular PDI regulates the expression and activity of the NADPH oxidase family of proteins (Nox), which are enzymes dedicated to ROS generation. PDI acts as a new organizer of leukocyte Nox2 by redox dependently associating with p47phox and controlling its recruitment to the plasma membrane, an essential step for assembly of the active enzyme. Such multiple effects of PDI suggest that specific targeting of this oxidoreductase could represent a new approach in the treatment of vascular disease. In this review, we present a novel role for PDI as an adaptor protein involved in redox processes and Nox signaling and propose PDI as a potential therapeutic target in the treatment of atherosclerosis, thrombosis and hypertension. (AU)

• Processo FAPESP: 09/54764-6 - Regulação da homeostase redox e resposta integrada a estresse pela dissulfeto isomerase protéica (PDI): mecanismos e papel na fisiopatologia e terapêutica de doenças vasculares
• Beneficiário: Francisco Rafael Martins Laurindo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/03520-5 - Papel da proteína dissulfeto isomerase na geração de espécies reativas de oxigênio pela NADPH oxidase durante o desenvolvimento da hipertensão arterial
• Beneficiário: Lucia Rossetti Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs