Angiotensin II type 1 receptor is involved in hypertension and vascular alterations caused by environmental toxicant hexachlorobenzene

Caimi, Giselle Romero; Gorzalczany, Susana; Bonazzola, Patricia; Deza, Zahira; Rosón, María Inés; Álvarez, Laura; Castilla, Rocı́o

doi:10.1016/j.toxrep.2021.08.009

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…They also reported that the expression of AT1R protein in the aorta was significantly reduced in the knockout mice indicating that AhR signaling might control the expression level of the AT1R protein. There are studies indicating that certain AhR agonists, such as indoxyl sulfate and hexachlorobenzene (HCB) induce hypertension and vascular dysfunctions in mice [135,174]. Sun et al [136] demonstrated that exposure to indoxyl sulfate activated the intrarenal RAAS involving an increase in the expression of renin, angiotensinogen, and AT1R proteins.…”

Section: Ahr Signaling Controls Blood Flow In Brain Via Renin-angiote...mentioning

confidence: 99%

Activation of aryl hydrocarbon receptor (AhR) in Alzheimer’s disease: role of tryptophan metabolites generated by gut host-microbiota

Salminen

2023

J Mol Med

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Gut microbiota in interaction with intestinal host tissues influences many brain functions and microbial dysbiosis has been linked with brain disorders, such as neuropsychiatric conditions and Alzheimer’s disease (AD). l-tryptophan metabolites and short-chained fatty acids (SCFA) are major messengers in the microbiota-brain axis. Aryl hydrocarbon receptors (AhR) are main targets of tryptophan metabolites in brain microvessels which possess an enriched expression of AhR protein. The Ah receptor is an evolutionarily conserved, ligand-activated transcription factor which is not only a sensor of xenobiotic toxins but also a pleiotropic regulator of both developmental processes and age-related tissue degeneration. Major microbiota-produced tryptophan metabolites involve indole derivatives, e.g., indole 3-pyruvic acid, indole 3-acetaldehyde, and indoxyl sulfate, whereas indoleamine and tryptophan 2,3-dioxygenases (IDO/TDO) of intestine host cells activate the kynurenine (KYN) pathway generating KYN metabolites, many of which are activators of AhR signaling. Chronic kidney disease (CKD) increases the serum level of indoxyl sulfate which promotes AD pathogenesis, e.g., it disrupts integrity of blood–brain barrier (BBB) and impairs cognitive functions. Activation of AhR signaling disturbs vascular homeostasis in brain; (i) it controls blood flow via the renin-angiotensin system, (ii) it inactivates endothelial nitric oxide synthase (eNOS), thus impairing NO production and vasodilatation, and (iii) it induces oxidative stress, stimulates inflammation, promotes cellular senescence, and enhances calcification of vascular walls. All these alterations are evident in cerebral amyloid angiopathy (CAA) in AD pathology. Moreover, AhR signaling can disturb circadian regulation and probably affect glymphatic flow. It seems plausible that dysbiosis of gut microbiota impairs the integrity of BBB via the activation of AhR signaling and thus aggravates AD pathology. Key messages Dysbiosis of gut microbiota is associated with dementia and Alzheimer’s disease. Tryptophan metabolites are major messengers from the gut host-microbiota to brain. Tryptophan metabolites activate aryl hydrocarbon receptor (AhR) signaling in brain. The expression of AhR protein is enriched in brain microvessels and blood-brain barrier. Tryptophan metabolites disturb brain vascular integrity via AhR signaling. Dysbiosis of gut microbiota promotes inflammation and AD pathology via AhR signaling.

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Section: Ahr Signaling Controls Blood Flow In Brain Via Renin-angiote...mentioning

confidence: 99%