Investigation of oxidative metabolism of uric acid and its role in redox processes in inflammation (2020)
- Authors:
- Autor USP: SILVA, RAILMARA PEREIRA DA - IQ
- Unidade: IQ
- Sigla do Departamento: QBQ
- DOI: 10.11606/T.46.2020.tde-29092021-142945
- Subjects: ÁCIDO ÚRICO; INFLAMAÇÃO; PSEUDOMONAS; PEROXIDASE
- Keywords: Ácido úrico; Hidroperóxido de urato; Infecção; Infection; Inflamação; Inflammation; Mieloperoxidase; Myeloperoxidase; Pseudomonas aeruginosa; Pseudomonas aeruginosa; Urate hydroperoxide; Uric acid
- Agências de fomento:
- Language: Inglês
- Abstract: This thesis studied the oxidation of uric acid during inflammation and its role in uric acid associated-pathologies . Uric acid is the end product of purine metabolism in humans and primates. Its concentration in plasma is higher than in other mammals, due to the repression of uricase gene. This repression was considered an evolutionary advantage since accumulation of uric acid in plasma increases the total blood antioxidant capacity. On the other hand, increased plasma uric acid has been associated with hypertension, gout, atherosclerosis and a worse prognosis in infection. Although the pathogenesis of these diseases is extremely complex and poorly understood, these associations suggest a causal role for uric acid. However, the exact mechanism for it is still unclear. Our group showed recently that uric acid is a substrate for myeloperoxidase, a heme-peroxidase abundant in neutrophils. The oxidation of uric acid by the enzyme generates urate free radical that combines with the radical anion superoxide to generate the oxidant urate hidroperoxide. Since chloride is the main substrate for myeloperoxidase, the present study aimed to investigate whether urate hidroperoxide would be formed during the oxidative burst in neutrophils. Through the sensitive liquid chromatography coupled to mass spectrometry method, we demonstrated the formation of urate hidroperoxide by peripheral blood neutrophils activated with phorbol miristate acetate, mimicking an inflammatory stimulus. Thus, we confirmed our hypothesis and demonstrated, for the first time, the formation of this new oxidant in inflammation. . The presence of uric acid during the inflammatory oxidative burst increased the oxidation of glutathione and the production of the radical anion superoxide, promoting a more oxidative environment. Besides the urate hydroperoxide, the oxidation of uric acid generates other intermediates that reactwith lysine residues to form covalencovalent adducts in albumin, a process named uratylation.. These urate covalent adducts, as well as the end product of uric acid oxidation, allantoin, were elevated in plasma albumin from patients with heart failure and diabetes. Therefore, allantoin and uratylated peptides from albumin could be useful biomarkers of inflammatory and cardiovascular diseases. The oxidation of uric acid by neutrophils decreases the production of hypochlorous acid due to the competition between uric acid and chloride by myeloperoxidase and this hinders the microbicide activity of these cells against Pseudomonas aeruginosa, as previously demonstrated by our group. In the present study we demonstrated that the oxidation of uric acid is also more pronounced in patients with septicaemia. There was a significant augment of plasma allantoin and an uratylated peptide from albumin in these patients compared to health individuals. By incubating peripheral blood neutrophils with uric acid and Pseudomonas aeruginosa we detected in increase in allantoin, in the oxidation of glutathione and glutathionylation of the microbicide protein calprotectin (S100A8). Uric acid also increased total neutrophil triacylglycerols (TAGs), including those sterified with araquidonic acid. These data suggest that, in infectious processes, uric acid may indirectly affect protein function through the induction of glutathionylation and can also remodel lipid constitution in inflammatory cells. These alterations may have a relevant role in the pathogenesis of sepsis and could explain, at least in part, the worse correlation between sepsis and higher levels of plasma uric acid.In this context, we propose the assessment of allantoin and uratylated albumin peptides as useful tools to monitor the progression of infectious and inflammatory diseases
- Imprenta:
- Data da defesa: 23.09.2020
- Este periódico é de acesso aberto
- Este artigo é de acesso aberto
- URL de acesso aberto
- Cor do Acesso Aberto: gold
- Licença: cc-by-nc-sa
-
ABNT
SILVA, Railmara Pereira da. Investigation of oxidative metabolism of uric acid and its role in redox processes in inflammation. 2020. Tese (Doutorado) – Universidade de São Paulo, São Paulo, 2020. Disponível em: https://www.teses.usp.br/teses/disponiveis/46/46131/tde-29092021-142945/. Acesso em: 02 maio 2024. -
APA
Silva, R. P. da. (2020). Investigation of oxidative metabolism of uric acid and its role in redox processes in inflammation (Tese (Doutorado). Universidade de São Paulo, São Paulo. Recuperado de https://www.teses.usp.br/teses/disponiveis/46/46131/tde-29092021-142945/ -
NLM
Silva RP da. Investigation of oxidative metabolism of uric acid and its role in redox processes in inflammation [Internet]. 2020 ;[citado 2024 maio 02 ] Available from: https://www.teses.usp.br/teses/disponiveis/46/46131/tde-29092021-142945/ -
Vancouver
Silva RP da. Investigation of oxidative metabolism of uric acid and its role in redox processes in inflammation [Internet]. 2020 ;[citado 2024 maio 02 ] Available from: https://www.teses.usp.br/teses/disponiveis/46/46131/tde-29092021-142945/ - Estudo dos produtos de oxidação do ácido úrico gerados através da reação com ácido hipocloroso
- Oxidação do ácido úrico e a modulação do perfil lipídico de neutrófilos infectados com Pseudomonas aeruginosa
- Uric acid reacts with peroxidasin, decreases collagen iv crosslink, impairs human endothelial cell migration and adhesion
- Estudo dos produtos de oxidação do ácido úrico gerados através do ácido hipocloroso
- Metabolismo oxidativo do ácido úrico e a relação com a progressão da sepse
- Laminin is the main brominated protein by hypobromous acid and Peroxidasin in the extracellular matrix
- AhpC1 aumenta a virulência da Pseudomonas aeruginosa através da redução de oxidantes gerados durante a inflamação
- Peroxiredoxin AhpC1 protects Pseudomonas aeruginosa against the inflammatory oxidative burst and confers virulence
- Development of a redox proteomics workflow to identify cell surface proteins susceptible to thiol oxidation in endothelial cells
- The antioxidant peroxiredoxin AhpC1 is a key protein in Pseudomonas aeruginosa virulence and in protection against oxidative response
Informações sobre o DOI: 10.11606/T.46.2020.tde-29092021-142945 (Fonte: oaDOI API)
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