A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides

Gonçalves-Dias, Clara; Sequeira, Catarina O.; Vicente, João B.; Correia, Maria João; Coelho, Nuno R.; Morelló, Judit; Antunes, Alexandra M. M.; Soto, Karina; Monteiro, Emília C.; Pereira, Sofia A.

doi:10.1007/978-3-030-63908-2_8

Cited by 3 publications

(3 citation statements)

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“…While more evidence is needed regarding cysteine [10,11,225,226], the renal tubular metabolism has recently emerged as a contributor to the long-term regulation of blood pressure (reviewed in Reference [80]). This metabolic perspective is co-substantiated by the impact on blood pressure that has been attributed to SGLT2 inhibitors [227], HIF stabilizers [228], gut-microbiota driven-metabolites (reviewed in References [227,229,230]) or to genome-wide association studies of environment-related metabolic pathways with high expression in kidney tubule, including the MAP [39] and the aryl-hydrocarbon receptor (AhR) circuitry [11,230,231]. Thus, more clinical and mechanistic studies are needed in interindividual variability in cysteine dynamics that may select patients more vulnerable to increased blood pressure and the cysteine-related thiolome might represent a reliable indicator of this vulnerability.…”

Section: Implications For Precision Medicine In Arterial Hypertension...mentioning

confidence: 99%

“…MAP is a hallmark of the kidney proximal tubular cells and is relevant for two reasons [16,17,38,39].…”

Section: Introductionmentioning

confidence: 99%

“…Cysteine is less likely than glutathione to remain reduced in an oxidative environment [47,48], and the formation of cysteine-S conjugates has been reported to be far more stable [49] and with higher half-lives than their precursors [50]. NAT8 is specialized in the control of cysteine-S conjugates, including CysSS and other cysteine disulfides [39,46,51], which are acetylated by NAT8 at the expense of acetyl coenzyme A (acetyl-CoA), rendering them prone to urinary elimination (Figure 1G). Importantly, polymorphisms in the NAT8 promotor are associated with systolic blood pressure and chronic kidney disease in hypertensive individuals [45,52,53].…”

Section: Introductionmentioning

confidence: 99%

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Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

et al. 2022

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In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.

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Section: Implications For Precision Medicine In Arterial Hypertension...mentioning

confidence: 99%

“…MAP is a hallmark of the kidney proximal tubular cells and is relevant for two reasons [16,17,38,39].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

et al. 2022

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Comprehensive analysis of the immunological differences in the intestinal barrier of improved grass carp and their parents

Tan,

Hu,

Liu

et al. 2023

Aquaculture

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

et al. 2021

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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.

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A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides

Cited by 3 publications

References 26 publications

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

Comprehensive analysis of the immunological differences in the intestinal barrier of improved grass carp and their parents

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

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