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Cysteine Oxidative Dynamics Underlies Hypertension and Kidney Dysfunction Induced by Chronic Intermittent Hypoxia

  • Nuno R. Coelho
  • Clara G. Dias
  • M. João Correia
  • Patrícia Grácio
  • Jacinta Serpa
  • Emília C. MonteiroEmail author
  • Lucília N. Diogo
  • Sofia A. Pereira
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1071)

Abstract

Previous data showed the lack of efficacy of an adrenoceptor antagonist to revert hypertension induced by chronic intermittent hypoxia (CIH). We hypothesized that, in addition to sympathetic activation, CIH may change the availability and dynamics of cysteine. Temporal variation in total cysteine and its fractions, free reduced, free oxidized and protein-bound (CysSSP), were measured in homogenates of kidney cortex and medulla of Wistar rats. Animals were exposed to CIH for 14, 21 and 60 days and cysteine fractions and fibronectin gene expression were assessed at these time-points. Two different phases in cysteine dynamics were identified. An early phase (14d) characterized by an increase in cysteine oxidation and CysSSP forms. Late events (>21d) were characterized by a global reduction in cysteine, minimum level of CysSSP and maximum overexpression of fibronectin in kidney cortex. In conclusion, cysteine dynamics is influenced by the duration of CIH exposure: first there is a cysteine disulfide stress-like adaptive response followed by a progressive loss of cysteine availability and a decrease in CysSSP fraction. Kidney fibrosis associated to an unbalance in cysteine dynamics might contribute to the inefficacy of available antihypertensive drugs in patients with delayed diagnosis of sleep apnea.

Keywords

Cysteine Protein S-cysteinylation Disulfide stress Kidney fibrosis Systemic hypertension Antihypertensive drug response 

Notes

Funding

iNOVA4Health – UID/Multi/04462/2013 (Ref: 201601-02-021).

FCT – PD/BD/114257/2016(NRC), PD/BD/105892/2014 (CGD) and SFRH/BD/130911/2017 (MJC).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Nuno R. Coelho
    • 1
  • Clara G. Dias
    • 1
  • M. João Correia
    • 1
  • Patrícia Grácio
    • 1
  • Jacinta Serpa
    • 1
    • 2
  • Emília C. Monteiro
    • 1
    Email author
  • Lucília N. Diogo
    • 1
  • Sofia A. Pereira
    • 1
  1. 1.CEDOC, Centro de Estudos Doenças Crónicas, Nova Medical School, Faculdade de Ciências MédicasUniversidade Nova de LisboaLisbonPortugal
  2. 2.Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG)LisbonPortugal

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