TY - JOUR
T1 - S-thiolation targets albumin in heart failure
AU - Brioschi, Maura
AU - Gianazza, Erica
AU - Mallia, Alice
AU - Zoanni, Beatrice
AU - Altomare, Alessandra
AU - Fernandez, Alma Martinez
AU - Agostoni, Piergiuseppe
AU - Aldini, Giancarlo
AU - Banfi, Cristina
N1 - Funding Information:
Funding: This work was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement number 675132 and by the Italian Ministry of Health, Rome, Italy (Ricerca Corrente RC 2019 MPP1A ID 2755301).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO2/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with H2O2, we showed a significant decrease of cell viability in cells treated with thioHSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression.
AB - Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO2/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with H2O2, we showed a significant decrease of cell viability in cells treated with thioHSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression.
KW - Albumin
KW - Heart failure
KW - Oxidative stress
KW - S-thiolation
UR - http://www.scopus.com/inward/record.url?scp=85090255222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090255222&partnerID=8YFLogxK
U2 - 10.3390/antiox9080763
DO - 10.3390/antiox9080763
M3 - Article
AN - SCOPUS:85090255222
VL - 9
SP - 1
EP - 13
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 8
M1 - 763
ER -