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

• Main Authors: Maria João Correia (Author), António B. Pimpão (Author), Filipa Lopes-Coelho (Author), Catarina O. Sequeira (Author), Nuno R. Coelho (Author), Clara Gonçalves-Dias (Author), Robert Barouki (Author), Xavier Coumoul (Author), Jacinta Serpa (Author), Judit Morello (Author), Emília C. Monteiro (Author), Sofia A. Pereira (Author)
• Format: Book
• Published: MDPI AG, 2021-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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-<i>S</i>-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 <i>Cyp1a1</i> 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.

Item Description

10.3390/antiox10091484
2076-3921