Peri/Epicellular Thiol Oxidoreductases as Mediators of Extracellular Redox Signaling

Author(s)

Tanaka, Leonardo Y. ^[1] ; Oliveira, Percillia V. S. ^[1] ; Laurindo, Francisco R. M. ^[1]

Affiliation

^[1] Univ Sao Paulo, LIM 64 Translat Cardiovasc Biol, Inst Coracao InCor, Hosp Clin HCFMUSP, Fac Med, Vasc Biol Lab, Ave Eneas C Aguiar 44 Annex 2, 9th Floor, BR-05403904 Sao Paulo - Brazil

• Document type: Journal article
• Source: Antioxidants & Redox Signaling; v. 33, n. 4 FEB 2020.
• Web of Science Citations: 0

Abstract

Recent Advances: pecTOR redox-modulates several targets including integrins, ECM proteins, surface molecules, and plasma components, although clear-cut documentation of direct effects is lacking in many cases. TOR catalytic pathways, displaying common patterns, culminate in substrate thiol reduction, oxidation, or isomerization. Peroxiredoxins act as redox/peroxide sensors, contrary to PDIs, which are likely substrate-targeted redox modulators. Emerging evidence suggests important pecTOR roles in patho(physio)logical processes, including blood coagulation, vascular remodeling, mechanosensing, endothelial function, immune responses, and inflammation. Critical Issues: Effects of pecPDIs supporting thrombosis/platelet activation have been well documented and reached the clinical arena. Roles of pecPDIA1 in vascular remodeling/mechanosensing are also emerging. Extracellular thioredoxin and pecPDIs redox-regulate immunoinflammation. Routes of TOR externalization remain elusive and appear to involve Golgi-independent routes. pecTORs are particularly accessible drug targets. Future Directions: Further understanding mechanisms of thiol redox reactions and developing assays for assessing pecTOR redox activities remain important research avenues. Also, addressing pecTORs as disease markers and achieving more efficient/specific drugs for pecTOR modulation are major perspectives for diagnostic/therapeutic improvements. (AU)

• FAPESP's process: 18/07230-5 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation
• Grantee: Leonardo Yuji Tanaka
• Support Opportunities: Research Grants - Young Investigators 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
• FAPESP's process: 19/03617-5 - Cytosolic Protein Disulfide Isomerase-A1 (PDIA1): a novel thiol-redox mechanism in cell signaling
• Grantee: Percíllia Victória Santos de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral