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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Protein Disulfide Isomerase and Nox: New Partners in Redox Signaling

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Author(s):
Trevelin, Silvia Cellone [1, 2] ; Lopes, Lucia Rossetti [1]
Total Authors: 2
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: CURRENT PHARMACEUTICAL DESIGN; v. 21, n. 41, p. 5951-5963, 2015.
Web of Science Citations: 17
Abstract

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)

FAPESP's process: 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases
Grantee:Francisco Rafael Martins Laurindo
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/03520-5 - Role of protein disulfide isomerase in NADPH oxidase dependent ROS generation during hypertension development
Grantee:Lucia Rossetti Lopes
Support Opportunities: Regular Research Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC