The constitutive androstane receptor and pregnane X receptor in the brain

Torres-Vergara, Pablo; Ho, Yu Siong; Espinoza, Francisca; Nualart, Francisco; Escudero, Carlos; Penny, Jeffrey

doi:10.1111/bph.15055

Cited by 18 publications

(16 citation statements)

References 142 publications

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“…However, the control of retinoid metabolism, inflammation, iron, glucose, lipid, cholesterol, bile acid, and bilirubin homeostasis, as well as the regulation of bone mineral density, were also demonstrated [ 19 , 70 , 75 , 76 ]. In this sense, mammalian pxr transcripts have also been detected in osteoblastic and neural cells, as well as in the endothelial cells of the blood-brain barrier (BBB) [ 17 , 18 , 19 , 77 ]. In fish, a broad distribution of pxr expression in tissues/organs was reported in different species [ 20 , 37 , 78 , 79 ].…”

Section: Vitamin K Molecular Pathwaysmentioning

confidence: 99%

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

2020

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Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways—the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins—have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate’s reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.

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Section: Vitamin K Molecular Pathwaysmentioning

confidence: 99%

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

2020

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“…Available data support the hypothesis that CAR functions may extend to a dialogue between multiple organs, perhaps including the central nervous system (Figure 2). The role of CAR could differ according to brain regions as suggested [134]. Furthermore, in the brain, CAR may be involved in the control of energy homeostasis through a cross-talk with the liver or the adipose tissue [13,87,133].…”

Section: Conclusion: Can We Integrate Car Within a Peripheral-brain mentioning

confidence: 99%

Constitutive Androstane Receptor: A Peripheral and a Neurovascular Stress or Environmental Sensor

Oliviero

Lukowicz

Boussadia

et al. 2020

Cells

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Xenobiotic nuclear receptors (NR) are intracellular players involved in an increasing number of physiological processes. Examined and characterized in peripheral organs where they govern metabolic, transport and detoxification mechanisms, accumulating data suggest a functional expression of specific NR at the neurovascular unit (NVU). Here, we focus on the Constitutive Androstane Receptor (CAR), expressed in detoxifying organs such as the liver, intestines and kidneys. By direct and indirect activation, CAR is implicated in hepatic detoxification of xenobiotics, environmental contaminants, and endogenous molecules (bilirubin, bile acids). Importantly, CAR participates in physiological stress adaptation responses, hormonal and energy homeostasis due to glucose and lipid sensing. We next analyze the emerging evidence supporting a role of CAR in NVU cells including the blood–brain barrier (BBB), a key vascular interface regulating communications between the brain and the periphery. We address the emerging concept of how CAR may regulate specific P450 cytochromes at the NVU and the associated relevance to brain diseases. A clear understanding of how CAR engages during pathological conditions could enable new mechanistic, and perhaps pharmacological, entry-points within a peripheral–brain axis.

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“…PXR is also observed in the THP1 cell line (acute monocytic leukemia) [35], in mouse peritoneal macrophages [39], mesenteric adipose tissue [40], and calvaria osteoblasts [41]. PXR and CAR expression profiles in placenta and brain have been reviewed recently [42,43].…”

Section: Pxr and Car Tissue Distributionmentioning

confidence: 99%

Regulation of CAR and PXR Expression in Health and Disease

Daujat-Chavanieu

Gerbal‐Chaloin

2020

Cells

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Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are members of the nuclear receptor superfamily that mainly act as ligand-activated transcription factors. Their functions have long been associated with the regulation of drug metabolism and disposition, and it is now well established that they are implicated in physiological and pathological conditions. Considerable efforts have been made to understand the regulation of their activity by their cognate ligand; however, additional regulatory mechanisms, among which the regulation of their expression, modulate their pleiotropic effects. This review summarizes the current knowledge on CAR and PXR expression during development and adult life; tissue distribution; spatial, temporal, and metabolic regulations; as well as in pathological situations, including chronic diseases and cancers. The expression of CAR and PXR is modulated by complex regulatory mechanisms that involve the interplay of transcription factors and also post-transcriptional and epigenetic modifications. Moreover, many environmental stimuli affect CAR and PXR expression through mechanisms that have not been elucidated.

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The constitutive androstane receptor and pregnane X receptor in the brain

Cited by 18 publications

References 142 publications

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

Constitutive Androstane Receptor: A Peripheral and a Neurovascular Stress or Environmental Sensor

Regulation of CAR and PXR Expression in Health and Disease

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