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. Monteiro, Lucília N. Diogo, Sofia A. Pereira

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages83-88
Number of pages6
DOIs
Publication statusPublished - 2018
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1071
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

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

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