Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells

Han, Zhiyi; Miwa, Yoshiro; Obikane, Hiyo; Mitsumata, Masako; Takahashi-Yanaga, Fumi; Morimoto, Sachio; Sasaguri, Toshiyuki

doi:10.1093/cvr/cvm095

Cited by 45 publications

(40 citation statements)

References 33 publications

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“…Although the specific mechanism by which CYP1A1 contributes to blood pressure regulation has not been fully elucidated, a number of studies suggest that it may play a role in the regulation of vascular tone. CYP1A1 is induced in endothelial cells by physiologic levels of laminar shear stress that stimulate flow-mediated vasodilation (Han et al, 2008;Conway et al, 2009). CYP1A1 also is expressed in mouse mesenteric resistance arterioles (Kopf et al, 2010), and CYP1A1-generated metabolites of EPA and DHA are potent vasodilators (Zhang et al, 2001;Ye et al, 2002;Hercule et al, 2007;Morin et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Role of CYP1A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Agbor

Wiest

Rothe

et al. 2014

J Pharmacol Exp Ther

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The mechanisms that mediate the cardiovascular protective effects of omega 3 (n-3) polyunsaturated fatty acids (PUFAs) have not been fully elucidated. Cytochrome P450 1A1 efficiently metabolizes n-3 PUFAs to potent vasodilators. Thus, we hypothesized that dietary n-3 PUFAs increase nitric oxide (NO)-dependent blood pressure regulation and vasodilation in a CYP1A1-dependent manner. CYP1A1 wild-type (WT) and knockout (KO) mice were fed an n-3 or n-6 PUFA-enriched diet for 8 weeks and were analyzed for tissue fatty acids and metabolites, NO-dependent blood pressure regulation, NO-dependent vasodilation of acetylcholine (ACh) in mesenteric resistance arterioles, and endothelial NO synthase (eNOS) and phospho-Ser1177-eNOS expression in the aorta. All mice fed the n-3 PUFA diet showed significantly higher levels of n-3 PUFAs and their metabolites, and significantly lower levels of n-6 PUFAs and their metabolites. In addition, KO mice on the n-3 PUFA diet accumulated significantly higher levels of n-3 PUFAs in the aorta and kidney without a parallel increase in the levels of their metabolites. Moreover, KO mice exhibited significantly less NO-dependent regulation of blood pressure on the n-3 PUFA diet and significantly less NO-dependent, ACh-mediated vasodilation in mesenteric arterioles on both diets. Finally, the n-3 PUFA diet significantly increased aortic phospho-Ser1177-eNOS/eNOS ratio in the WT compared with KO mice. These data demonstrate that CYP1A1 contributes to eNOS activation, NO bioavailability, and NO-dependent blood pressure regulation mediated by dietary n-3 PUFAs.

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Section: Discussionmentioning

confidence: 99%

Role of CYP1A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Agbor

Wiest

Rothe

et al. 2014

J Pharmacol Exp Ther

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“…An anti-BrdU monoclonal detector antibody was incubated with the cells for 1 h, followed by horseradish peroxidase-conjugated goat anti-mouse antibody for 30 min at room temperature. After treatment with the chromogenic substrate tetramethylbenzidine (TMB) and addition of stop solution, the amount of BrdU was quantified spectrophotometrically with a microplate spectrophotometer at a wavelength of 450 nm, with a reference wavelength of 570 nm (23).…”

Section: Methodsmentioning

confidence: 99%

Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

et al. 2012

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f Enterococcus faecalis is a member of the intestinal and oral microbiota that may affect the etiology of colorectal and oral cancers. The mechanisms by which E. faecalis may contribute to the initiation and progression of these cancers remain uncertain. Epidermal growth factor receptor (EGFR) signaling is postulated to play a crucial role in oral carcinogenesis. A link between E. faecalis and EGFR signaling in oral cancer has not been elucidated. The present study aimed to evaluate the association between E. faecalis and oral cancer and to determine the underlying mechanisms that link E. faecalis to EGFR signaling. We report the high frequency of E. faecalis infection in oral tumors and the clinical association with EGFR activation. Using human oral cancer cells, we support the clinical findings and demonstrate that E. faecalis can induce EGFR activation and cell proliferation. E. faecalis activates EGFR through production of H 2 O 2 , a signaling molecule that activates several signaling pathways. Inhibitors of H 2 O 2 (catalase) and EGFR (gefitinib) significantly blocked E. faecalis-induced EGFR activation and cell proliferation. Therefore, E. faecalis infection of oral tumor tissues suggests a possible association between E. faecalis infection and oral carcinogenesis. Interaction of E. faecalis with host cells and production of H 2 O 2 increase EGFR activation, thereby contributing to cell proliferation.

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“…However, the possibility that AHR ligands are present in these cells cannot be excluded. Shear stress in endothelial cells can also lead to AHR activation, although the mechanism of activation is not known 19, 20 . Co-expression of a mutant AHR unable to bind ligand (AhR-A375I) and ARNT increased AHR-mediated transcriptional activity suggests that the AHR can potentially heterodimerize with ARNT in the absence of ligand, although heterodimerization potential appear to be quite inefficient 21 .…”

Section: Mechanisms Of Ahr Activationmentioning

confidence: 99%

Aryl hydrocarbon receptor ligands in cancer: friend and foe

2014

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Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells

Cited by 45 publications

References 33 publications

Role of CYP1A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Role of CYP1A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

Aryl hydrocarbon receptor ligands in cancer: friend and foe

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