Angiotensin AT2 receptor activates the cyclic-AMP signaling pathway in eel

Wong, Marty Kwok‐Shing; Takei, Yoshiyuki

doi:10.1016/j.mce.2012.11.009

Cited by 19 publications

(9 citation statements)

References 43 publications

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“…Zebrafish has a single ortholog of human AGTR2 with conserved syntenies (Fig. 3G) (Wong and Takei, 2013). In situ hybridization identified agtr2 (ENSDARG00000035552) expression in zebrafish endothelia (Wong et al, 2009), which the Atlas confirmed ( Fig.…”

Section: Resultsmentioning

confidence: 87%

An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities

Farnsworth

Miller

2020

Preprint

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People with underlying conditions, including hypertension, obesity, and diabetes, are especially susceptible to negative outcomes after infection with the coronavirus SARS-CoV-2. These COVID-19 comorbidities are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from rapidly dropping blood pressure or dehydration via the peptide Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II, thus counteracting its chronic effects. Ace2 is also the SARS-CoV-2 receptor. Ace, the coronavirus, and COVID-19 comorbidities all regulate Ace2, but we don’t yet understand how. To exploit zebrafish (Danio rerio) as a disease model to understand mechanisms regulating the RAAS and its relationship to COVID-19 comorbidities, we must first identify zebrafish orthologs and co-orthologs of human RAAS genes, and second, understand where and when these genes are expressed in specific cells in zebrafish development. To achieve these goals, we conducted genomic analyses and investigated single cell transcriptomes. Results showed that most human RAAS genes have an ortholog in zebrafish and some have two or more co-orthologs. Results further identified a specific intestinal cell type in zebrafish larvae as the site of expression for key RAAS components, including Ace, Ace2, the coronavirus co-receptor Slc6a19, and the Angiotensin-related peptide cleaving enzymes Anpep and Enpep. Results also identified specific vascular cell subtypes as expressing Ang II receptors, apelin, and apelin receptor genes. These results identify specific genes and cell types to exploit zebrafish as a disease model for understanding the mechanisms leading to COVID-19 comorbidities.SUMMARY STATEMENTGenomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics show that they act in a specialized intestinal cell type.

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Section: Resultsmentioning

confidence: 87%

An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities

Farnsworth

Miller

2020

Preprint

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“…However, no clear staining was observed (Y Kumai and S F Perry, unpublished observations) and to our knowledge there is no commercial antibody able to recognize the zebrafish ANG-II receptor. Wong & Takei (2013) recently have reported the sequence of the AT 2 receptor from A. japonica and observed its high expression in spleen and gill; no particularly strong staining was observed in branchial ionocytes based on in situ hybridization. Because the same study suggested the presence of an AT 2 -like gene in zebrafish based on sequence analysis, it is possible that AT 2 is also involved with Na C uptake regulation in zebrafish larvae.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-II promotes Na+ uptake in larval zebrafish, Danio rerio, in acidic and ion-poor water

Kumai

Bernier

Perry

2013

Journal of Endocrinology

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The contribution of the renin-angiotensin system (RAS) to Na C uptake was investigated in larval zebrafish (Danio rerio). At 4 days post fertilization (dpf), the level of whole-body angiotensin-II (ANG-II) was significantly increased after 1-or 3-h exposure to acidic (pHZ4.0) or ion-poor water (20-fold dilution of Ottawa tapwater), suggesting rapid activation of the RAS. Long-term (24 h) treatment of 3 dpf larvae with ANG-I or ANG-II significantly increased Na C uptake which was accompanied by an increase in mRNA expression of the NaInduction of Na C uptake by exposure to ANG-I was blocked by simultaneously treating larvae with lisinopril (an angiotensin-converting enzyme inhibitor). Acute (2 h) exposure to acidic water or ion-poor water led to significant increase in Na C uptake which was partially blocked by the ANG-II receptor antagonist, telmisartan. Consistent with these data, translational knockdown of renin prevented the stimulation of Na C uptake following exposure to acidic or ion-poor water. The lack of any effects of pharmacological inhibition (using RU486), or knockdown of glucocorticoid receptors on the stimulation of Na C uptake during acute exposure to acidic or ion-poor environments, indicates that the acute effects of RAS occur independently of cortisol signaling. The results of this study demonstrate that the RAS is involved in Na C homeostasis in larval zebrafish. Key Words" angiotensin-II" cortisol " zebrafish " osmoregulation " ion-poor water " acidic water

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“…The cell suspension was centrifuged at 200 g for 10 min at 25°C, and the supernatant was then discarded. The cell pellet was washed twice using complete EMEM, and the cell density was adjusted to 5×10 6 cells/mL for subsequent experiments [19]. …”

Section: Methodsmentioning

confidence: 99%

Up-Regulated ATF4 Expression Increases Cell Sensitivity to Apoptosis in Response to Radiation

Zong

Feng

Cheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family which regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses. ATF4 is also over-expressed in human solid tumors, although its effect on responsiveness to radiation is largely unexplored. Methods: Real-time PCR was used to detect ATF4 mRNA levels in cells treated with different doses of ⁶⁰Coγ radiation. Cell viability was assayed using a cell counting kit. The cell cycle was analyzed using flow cytometry, and cell apoptosis was assayed using Annexin V-PI double labeling. Small interfering RNA (siRNA) against ATF4 was transfected into ECV304 cells using Lipofectamine 2000. An ATF4 over-expression plasmid (p-ATF4-CGN) was transfected into HEK293 cells that endogenously expressed low levels of ATF4. The levels of intracellular reactive oxygen species (ROS) were measured using CM-H2DCFDA as a probe. Results: ATF4 mRNA and protein expression levels were higher after radiation and increased in a dose- and time-dependent manner in AHH1 lymphoblast cells (P < 0.05). An increase in ATF4 levels was also observed after radiation in primary murine spleen cells, human endothelial ECV304 cells, human liver LO2 cells, breast cancer MCF7 cells, and human hepatocellular carcinoma HEPG2 cells. No change was observed in human embryonic kidney 293 (HEK293) cells. Over-expressing ATF4 in HEK293 cells inhibited cell proliferation, increased cell apoptosis and significantly increased the proportion of cells in G1 phase. Conversely, when ATF4 expression was knocked down using siRNA in ECV304 cells, it protected the cells from radiation-induced apoptosis. These findings suggest that ATF4 may play a role in radiation-induced cell killing by inhibiting cell proliferation and promoting cell apoptosis. Conclusions: In this study, we found that radiation up-regulated the expression of ATF4. We used ATF4 knockdown and over-expression systems to show that ATF4 may play a role in radiation-induced cellular apoptosis.

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Angiotensin AT2 receptor activates the cyclic-AMP signaling pathway in eel

Cited by 19 publications

References 43 publications

An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities

An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities

Angiotensin-II promotes Na+ uptake in larval zebrafish, Danio rerio, in acidic and ion-poor water

Up-Regulated ATF4 Expression Increases Cell Sensitivity to Apoptosis in Response to Radiation

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