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

• Published in: Antioxidants Vol. 10; no. 9; p. 1484
• Main Authors: Correia, Maria João, Pimpão, António B., Lopes-Coelho, Filipa, Sequeira, Catarina O., Coelho, Nuno R., Gonçalves-Dias, Clara, Barouki, Robert, Coumoul, Xavier, Serpa, Jacinta, Morello, Judit, Monteiro, Emília C., Pereira, Sofia A.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 17.09.2021; MDPI
• Subjects: Acids; Antibodies; Apnea; arterial hypertension; Biochemistry, Molecular Biology; Cardiology and cardiovascular system; Cell cycle; Creatinine; CYP1A1; Cysteine; Cytochrome P450; Endothelial cells; Free radicals; Genes; Human health and pathology; Hydrocarbons; Hypoxia; Kidneys; Laboratory animals; Life Sciences; Ligands; non-radical oxidative species; obstructive sleep apnea; Oxidative stress; Phenotypes; Precision medicine; Proteins; Reagents; Renal cortex; Sleep apnea; Sleep disorders; Sodium; thiols; Tissues and Organs; xCT; France; United States > US; Germany; obstructive sleep apnea; arterial hypertension; animal models; cystine; CYP1A1; xCT; precision medicine; thiols; non-radical oxidative species; endothelial dysfunction
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox10091484

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.