A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides

Clara Gonçalves-Dias; Catarina O. Sequeira; João B. Vicente; M. João Correia; Nuno R. Coelho; Judit Morello; Alexandra M.M. Antunes; Karina Soto; Emília C. Monteiro; Sofia A. Pereira

doi:10.1007/978-3-030-63908-2_8

A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides

Clara Gonçalves-Dias, Catarina O. Sequeira, João B. Vicente, M. João Correia, Nuno R. Coelho, Judit Morello, Alexandra M.M. Antunes, Karina Soto, Emília C. Monteiro, Sofia A. Pereira

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Our general goal was to non-invasively evaluate kidney tubular dysfunction. We developed a strategy based on cysteine (Cys) disulfide stress mechanism that underlies kidney dysfunction. There is scarce information regarding the fate of Cys-disulfides (CysSSX), but evidence shows they might be detoxified in proximal tubular cells by the action of N-acetyltransferase 8 (NAT8). This enzyme promotes the addition of an N-acetyl moiety to cysteine-S-conjugates, forming mercapturates that are eliminated in urine. Therefore, we developed a strategy to quantify mercapturates of CysSSX in urine as surrogate of disulfide stress and NAT8 activity in kidney tubular cells. We use a reduction agent for the selective reduction of disulfide bonds. The obtained N-acetylcysteine moiety of the mercapturates from cysteine disulfides was monitored by fluorescence detection. The method was applied to urine from mice and rat as well as individuals with healthy kidney and kidney disease.

Idioma original	???core.languages.en_GB???
Título da publicação do anfitrião	Advances in Experimental Medicine and Biology
Editora	Springer
Páginas	109-120
Número de páginas	12
DOIs	https://doi.org/10.1007/978-3-030-63908-2_8
Estado da publicação	???researchoutput.status.published??? - 2021
Publicado externamente	Sim

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Nome	Advances in Experimental Medicine and Biology
Volume	1306
ISSN (impresso)	0065-2598
ISSN (eletrónico)	2214-8019

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Gonçalves-Dias, C., Sequeira, C. O., Vicente, J. B., Correia, M. J., Coelho, N. R., Morello, J., Antunes, A. M. M., Soto, K., Monteiro, E. C., & Pereira, S. A. (2021). A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides. Em Advances in Experimental Medicine and Biology (pp. 109-120). (Advances in Experimental Medicine and Biology; Vol. 1306). Springer. https://doi.org/10.1007/978-3-030-63908-2_8

@inbook{7a367f9a447c4dce81afc81f5d9c8dbb,

title = "A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides",

abstract = "Our general goal was to non-invasively evaluate kidney tubular dysfunction. We developed a strategy based on cysteine (Cys) disulfide stress mechanism that underlies kidney dysfunction. There is scarce information regarding the fate of Cys-disulfides (CysSSX), but evidence shows they might be detoxified in proximal tubular cells by the action of N-acetyltransferase 8 (NAT8). This enzyme promotes the addition of an N-acetyl moiety to cysteine-S-conjugates, forming mercapturates that are eliminated in urine. Therefore, we developed a strategy to quantify mercapturates of CysSSX in urine as surrogate of disulfide stress and NAT8 activity in kidney tubular cells. We use a reduction agent for the selective reduction of disulfide bonds. The obtained N-acetylcysteine moiety of the mercapturates from cysteine disulfides was monitored by fluorescence detection. The method was applied to urine from mice and rat as well as individuals with healthy kidney and kidney disease.",

keywords = "Cysteine, Disulfide stress, Kidney function marker, Mercapturate pathway, Mercapturic acid, N-acetyltransferase-8, Proximal tubular cell, Uremic toxins",

author = "Clara Gon{\c c}alves-Dias and Sequeira, {Catarina O.} and Vicente, {Jo{\~a}o B.} and Correia, {M. Jo{\~a}o} and Coelho, {Nuno R.} and Judit Morello and Antunes, {Alexandra M.M.} and Karina Soto and Monteiro, {Em{\'i}lia C.} and Pereira, {Sofia A.}",

note = "Publisher Copyright: {\textcopyright} 2021, Springer Nature Switzerland AG.",

year = "2021",

doi = "10.1007/978-3-030-63908-2_8",

language = "English",

series = "Advances in Experimental Medicine and Biology",

publisher = "Springer",

pages = "109--120",

booktitle = "Advances in Experimental Medicine and Biology",

address = "Germany",

}

Gonçalves-Dias, C, Sequeira, CO, Vicente, JB, Correia, MJ, Coelho, NR, Morello, J, Antunes, AMM, Soto, K, Monteiro, EC & Pereira, SA 2021, A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides. em Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology, vol. 1306, Springer, pp. 109-120. https://doi.org/10.1007/978-3-030-63908-2_8

A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides. / Gonçalves-Dias, Clara; Sequeira, Catarina O.; Vicente, João B. et al.
Advances in Experimental Medicine and Biology. Springer, 2021. p. 109-120 (Advances in Experimental Medicine and Biology; Vol. 1306).

Resultado de pesquisa: ???type-name??? › ???researchoutput.researchoutputtypes.contributiontobookanthology.chapter??? › revisão de pares

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T1 - A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides

AU - Gonçalves-Dias, Clara

AU - Sequeira, Catarina O.

AU - Vicente, João B.

AU - Correia, M. João

AU - Coelho, Nuno R.

AU - Morello, Judit

AU - Antunes, Alexandra M.M.

AU - Soto, Karina

AU - Monteiro, Emília C.

AU - Pereira, Sofia A.

PY - 2021

Y1 - 2021

N2 - Our general goal was to non-invasively evaluate kidney tubular dysfunction. We developed a strategy based on cysteine (Cys) disulfide stress mechanism that underlies kidney dysfunction. There is scarce information regarding the fate of Cys-disulfides (CysSSX), but evidence shows they might be detoxified in proximal tubular cells by the action of N-acetyltransferase 8 (NAT8). This enzyme promotes the addition of an N-acetyl moiety to cysteine-S-conjugates, forming mercapturates that are eliminated in urine. Therefore, we developed a strategy to quantify mercapturates of CysSSX in urine as surrogate of disulfide stress and NAT8 activity in kidney tubular cells. We use a reduction agent for the selective reduction of disulfide bonds. The obtained N-acetylcysteine moiety of the mercapturates from cysteine disulfides was monitored by fluorescence detection. The method was applied to urine from mice and rat as well as individuals with healthy kidney and kidney disease.

AB - Our general goal was to non-invasively evaluate kidney tubular dysfunction. We developed a strategy based on cysteine (Cys) disulfide stress mechanism that underlies kidney dysfunction. There is scarce information regarding the fate of Cys-disulfides (CysSSX), but evidence shows they might be detoxified in proximal tubular cells by the action of N-acetyltransferase 8 (NAT8). This enzyme promotes the addition of an N-acetyl moiety to cysteine-S-conjugates, forming mercapturates that are eliminated in urine. Therefore, we developed a strategy to quantify mercapturates of CysSSX in urine as surrogate of disulfide stress and NAT8 activity in kidney tubular cells. We use a reduction agent for the selective reduction of disulfide bonds. The obtained N-acetylcysteine moiety of the mercapturates from cysteine disulfides was monitored by fluorescence detection. The method was applied to urine from mice and rat as well as individuals with healthy kidney and kidney disease.

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KW - Disulfide stress

KW - Kidney function marker

KW - Mercapturate pathway

KW - Mercapturic acid

KW - N-acetyltransferase-8

KW - Proximal tubular cell

KW - Uremic toxins

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U2 - 10.1007/978-3-030-63908-2_8

DO - 10.1007/978-3-030-63908-2_8

M3 - Chapter

C2 - 33959909

AN - SCOPUS:85105505491

T3 - Advances in Experimental Medicine and Biology

SP - 109

EP - 120

BT - Advances in Experimental Medicine and Biology

PB - Springer

ER -

A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides

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