Catalase post-translational modifications as key targets in the control of erythrocyte redox homeostasis in children with obesity and insulin resistance.

Autor: González-Domínguez Á; Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain. Electronic address: alvaro.gonzalez@inibica.com., Visiedo F; Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain. Electronic address: franciscom.visiedo@inibica.es., Domínguez-Riscart J; Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain; Pediatric Endocrinology and Diabetes, Department of Pediatrics, Puerta del Mar University Hospital, 11009, Cádiz, Spain. Electronic address: jesus.dominguezriscart@gmail.com., Durán-Ruiz MC; Cardiovascular regenerative therapy and applied proteomics. Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain; Area of Biochemistry and Molecular Biology, Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, 11519, Cádiz, Spain. Electronic address: maricarmen.duran@gm.uca.es., Saez-Benito A; Diabetes Mellitus-Autoimmunity and Chronic Complications. Pathological, clinical and therapeutic Implications. Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain; Clinical Analysis Department, Puerta del Mar University Hospital, 11009, Cádiz, Spain. Electronic address: anasaezbenito@gmail.com., Lechuga-Sancho AM; Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain; Pediatric Endocrinology and Diabetes, Department of Pediatrics, Puerta del Mar University Hospital, 11009, Cádiz, Spain; Area of Pediatrics, Department of Child and Mother Health and Radiology, Medical School, University of Cádiz, 11003, Cádiz, Spain. Electronic address: alfonso.lechuga@uca.es., Mateos RM; Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009, Cádiz, Spain; Area of Biochemistry and Molecular Biology, Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, 11519, Cádiz, Spain. Electronic address: rosa.mateos@uca.es.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2022 Oct; Vol. 191, pp. 40-47. Date of Electronic Publication: 2022 Aug 28.
DOI: 10.1016/j.freeradbiomed.2022.08.017
Abstrakt: Insulin resistance (IR) is the most common metabolic disturbance in children with obesity. Children with obesity and insulin resistance (ObIR+) display a detriment in erythroid antioxidant defenses, caused by an impaired catalase activity and the increase in oxidative and pro-inflammatory markers. Therefore, erythrocytes from ObRI+ are more vulnerable to any oxidative stress elicitor. Since catalase is one of the erythrocytes' first antioxidant defenses, we intended to delve into the mechanisms underlying catalase's impaired activity. Given the lack of cellular organelles in erythrocytes, which prevents protein synthesis, we aimed study catalase post-translational modifications (PTMs) as targets of pro-inflammatory and pro-oxidant status of these cells in children with obesity and IR. Catalase levels of O-glycosylation, tyrosine nitration and S-glutathionylation were analyzed by Western blotting (WB) using immunoprecipitated catalase (IP-CAT) from erythrocyte lysates. Furthermore, Catalase was also identified by LC-MS/MS after isolation and enrichment of erythrocyte nitrosated proteins with a biotin switch approach. The results obtained suggest that catalase inhibition seen in children with obesity is partly due to the increase in the S-nitrosation of the enzyme. Indeed, exogenous administration of nitric oxide (NO) to cultured erythrocytes resulted in a decrease in catalase activity in all groups. Signals of other PTMs (O-glycosylation, Tyr-nitration and S-glutathionylation) were also detected in the erythrocyte catalase in every groups, although levels of catalase O-glycosylation and S-glutathionylation decreased in ObIR+. No evidence of differences in Tyr-nitration of catalase levels were found among groups. The study again highlights the role of erythrocytes as sensors of the inflammatory and pro-oxidant response to which these cells are subjected in children with obesity and insulin resistance.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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