Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex

被引:9
|
作者
Correia, Maria Joao [1 ]
Pimpao, Antonio B. [1 ]
Lopes-Coelho, Filipa [1 ,2 ]
Sequeira, Catarina O. [1 ]
Coelho, Nuno R. [1 ]
Goncalves-Dias, Clara [1 ]
Barouki, Robert [3 ]
Coumoul, Xavier [3 ]
Serpa, Jacinta [1 ,2 ]
Morello, Judit [1 ]
Monteiro, Emilia C. [1 ]
Pereira, Sofia A. [1 ]
机构
[1] Univ Nova Lisboa, NOVA Med Sch, CEDOC, P-1169056 Lisbon, Portugal
[2] Inst Portugues Oncol Lisboa Francisco Gentil IPOL, Rua Prof Lima Basto, P-1099023 Lisbon, Portugal
[3] Univ Paris, INSERM UMR S 1124, 3TS, Environm Tox Therapeut Targets Cellular Signaling, 45 Rue St Peres, F-75006 Paris, France
关键词
thiols; non-radical oxidative species; obstructive sleep apnea; arterial hypertension; xCT; cystine; precision medicine; animal models; endothelial dysfunction; OBSTRUCTIVE SLEEP-APNEA; INDUCED RENAL INJURY; OXIDATIVE STRESS; INDOXYL SULFATE; CARDIOVASCULAR-DISEASE; THIOL/DISULFIDE REDOX; MOLECULAR-MECHANISMS; ENDOTHELIAL-CELLS; CYSTINE UPTAKE; NITRIC-OXIDE;
D O I
10.3390/antiox10091484
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and 21 days, pre-HTN), and long-term intermittent hypoxia (IH) (up to 60 days, established HTN) on CYP1A1 protein level (a sensitive hallmark of AhR activation) and cysteine-related thiol pools. We found that acute and chronic IH had opposite effects on CYP1A1 and the thiolome. While short-term IH decreased CYP1A1 and increased protein-S-thiolation, long-term IH increased CYP1A1 and free oxidized cysteine. In addition, an in vitro administration of cystine, but not cysteine, to human endothelial cells increased Cyp1a1 expression, supporting cystine as a putative AhR activator. This study supports CYP1A1 as a biomarker of obstructive sleep apnea (OSA) severity and oxidized pools of cysteine as risk indicator of OSA-HTN. This work contributes to a better understanding of the mechanisms underlying the phenotype of OSA-HTN, mimicked by this model, which is in line with precision medicine challenges in OSA.
引用
收藏
页数:22
相关论文
共 3 条
  • [1] Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease
    Curran, Colleen S.
    Kopp, Jeffrey B.
    FRONTIERS IN PHARMACOLOGY, 2022, 13
  • [2] Cysteine Oxidative Dynamics Underlies Hypertension and Kidney Dysfunction Induced by Chronic Intermittent Hypoxia
    Coelho, Nuno R.
    Dias, Clara G.
    Joao Correia, M.
    Gracio, Patricia
    Serpa, Jacinta
    Monteiro, Emilia C.
    Diogo, Lucilia N.
    Pereira, Sofia A.
    ARTERIAL CHEMORECEPTORS: NEW DIRECTIONS AND TRANSLATIONAL PERSPECTIVES, 2018, 1071 : 83 - 88
  • [3] First evidence of aryl hydrocarbon receptor as a druggable target in hypertension induced by chronic intermittent hypoxia
    Coelho, Nuno R.
    Tomkiewicz, Celine
    Correia, M. Joao
    Goncalves-Dias, Clara
    Barouki, Robert
    Pereira, Sofia A.
    Coumoul, Xavier
    Monteiro, Emilia C.
    PHARMACOLOGICAL RESEARCH, 2020, 159