Implications of plasma thiol redox in disease

Author(s)

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

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Biol Vasc, Inst Coracao InCor, Sao Paulo, SP - Brazil

• Document type: Review article
• Source: Clinical Science; v. 132, n. 12, p. 1257-1280, JUN 29 2018.
• Web of Science Citations: 11

Abstract

Thiol groups are crucially involved in signaling/homeostasis through oxidation, reduction, and disulphide exchange. The overall thiol pool is the resultant of several individual pools of small compounds (e.g. cysteine), peptides (e.g. glutathione), and thiol proteins (e.g. thioredoxin (Trx)), which are not in equilibrium and present specific oxidized/reduced ratios. This review addresses mechanisms and implications of circulating plasma thiol/disulphide redox pools, which are involved in several physiologic processes and explored as disease biomarkers. Thiol pools are regulated by mechanisms linked to their intrinsic reactivity against oxidants, concentration of antioxidants, thiol-disulphide exchange rates, and their dynamic release/removal from plasma. Major thiol couples determining plasma redox potential (Eh) are reduced cysteine (CyS)/cystine (the disulphide form of cysteine) (CySS), followed by GSH/disulphide-oxidized glutathione (GSSG). Hydrogen peroxide and hypohalous acids are the main plasma oxidants, while water-soluble and lipid-soluble small molecules are the main antioxidants. The thiol proteome and thiol-oxidoreductases are emerging investigative areas given their specific disease-related responses (e.g. protein disulphide isomerases (PDIs) in thrombosis). Plasma cysteine and glutathione redox couples exhibit pro-oxidant changes directly correlated with ageing/age-related diseases. We further discuss changes in thiol-disulphide redox state in specific groups of diseases: cardiovascular, cancer, and neurodegenerative. These results indicate association with the disease states, although not yet clear-cut to yield specific biomarkers. We also highlight mechanisms whereby thiol pools affect atherosclerosis pathophysiology. Overall, it is unlikely that a single measurement provides global assessment of plasma oxidative stress. Rather, assessment of individual thiol pools and thiol-proteins specific to any given condition has more solid and logical perspective to yield novel relevant information on disease risk and prognosis. (AU)

• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/20595-1 - Protein Disulfide Isomerase (PDI) as a marker of risk for thrombosis and/or accelerated progression of atherosclerosis in patients with familial hipercholesterolemia and in experimental model
• Grantee: Percíllia Victória Santos de Oliveira
• Support type: Scholarships in Brazil - Doctorate (Direct)