Produção Nacional
Revisado por pares
The Meaning of Mas
2018; Lippincott Williams & Wilkins; Volume: 72; Issue: 5 Linguagem: Inglês
10.1161/hypertensionaha.118.10918
ISSN1524-4563
AutoresMichael Bäder, Natália Alenina, Dallan Young, Robson A.S. Santos, Rhian M. Touyz,
Tópico(s)Receptor Mechanisms and Signaling
ResumoHomeHypertensionVol. 72, No. 5The Meaning of Mas Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBThe Meaning of Mas Michael Bader, Natalia Alenina, Dallan Young, Robson A.S. Santos and Rhian M. Touyz Michael BaderMichael Bader From the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany (M.B., N.A.) Charité–University Medicine, Berlin, Germany (M.B.) German Center for Cardiovascular Research, Berlin Partner Site (M.B., N.A.) Berlin Institute of Health, Germany (M.B.) Institute for Biology, University of Lübeck, Germany (M.B.) , Natalia AleninaNatalia Alenina From the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany (M.B., N.A.) German Center for Cardiovascular Research, Berlin Partner Site (M.B., N.A.) , Dallan YoungDallan Young Biochemistry and Molecular Biology, University of Calgary, Canada (D.Y.) , Robson A.S. SantosRobson A.S. Santos Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil (R.A.S.S.) and Rhian M. TouyzRhian M. Touyz Correspondence to Rhian M. Touyz, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Pl, Glasgow G12 8TA, United Kingdom. Email E-mail Address: [email protected] Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (R.M.T.). Originally published24 Sep 2018https://doi.org/10.1161/HYPERTENSIONAHA.118.10918Hypertension. 2018;72:1072–1075Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 24, 2018: Ahead of Print In the early 1980s, in their search for systems that import proteins into mitochondria, Yaffe and Schatz1 identified a mutant in the yeast Saccharomyces cerevisiae, mas1 (mitochondrial assembly 1), that accumulates mitochondrial precursor proteins (Table). In 1988, they cloned and sequenced the wild-type yeast MAS1 gene (systematic name: YLR163C), which encodes the catalytic subunit of the mitochondrial processing protease—a component of the mitochondrial import pathway and essential for cell viability.2 Later, homologs of this gene were found in other eukaryotes, including humans, in which the gene was called PMPCB.3 Around the same time, in 1986, a new gene was isolated from DNA of a human epidermoid carcinoma cell line, identified as a proto-oncogene, and named MAS.4 Initially, the function of the MAS protein was unknown, and it was only in the early 2000s that it was identified as the GPCR (G-protein–coupled receptor) through which Ang (angiotensin)-(1–7) signals. Unfortunately, the MAS gene was later renamed by the HUGO (Human Genome Organisation) Human Gene Nomenclature Committee to MAS1 (full name: MAS1 proto-oncogene, GPCR), and also in mouse, rat, and all other tetrapods, it got the new name Mas1. Fortunately, MAS is still an accepted alias of the MAS1 proto-oncogene protein, and we will use this name in the following article to distinguish it from the yeast Mas1 protein. We would also like to suggest that the name MAS should be used in future publications. There is no homolog of MAS in any clade outside tetrapods.5 However, several homologous genes were discovered in each tetrapod species, and the name MAS was given to this new family of receptors, the Mrgprs (Mas-related GPCRs).5,6Table. Comparison of Different MAS1 GenesOrganismGeneProteinAliasesFull NameDatabase IDsMolecular MassFunctionHumanMAS1MAS1MASMAS1 proto-oncogene, GPCRNCBI: 4142; HGNC: 689937 kDAGPCR, Ang-(1–7) receptorMouseMas1MAS1Mas, MasR, Mas-1MAS1 oncogeneNCBI: 17171; MGI: 9691837 kDAYeastMAS1Mas1pMas1, YLR163C, MIFMitochondrial assembly protein 1NCBI: 850860; SGD: S00000415351 kDACatalytic subunit of the mitochondrial processing proteaseStreptomyces sp. W007mas1 (SPW_1544)Mas1H0B8D4Marine streptomyces 1Uniprot: H0B8D431 kDaPutative secreted thermostable lipaseThe rules for the nomenclature of genes and proteins differ between organisms. In humans (https://www.genenames.org/about/guidelines), both are in uppercase letters, and gene symbols are italicized. In rats and mice (http://www.informatics.jax.org/mgihome/nomen/gene.shtml#pon), only protein symbols are in uppercase letters, and gene symbols have only an initial uppercase letter and are also italicized. In yeast, gene symbols are in uppercase, italicized letters, and proteins are referred to by the relevant gene symbol, nonitalic, only initial letter uppercase, and with the suffix p, which can be omitted when the context reveals that the protein is meant (http://seq.yeastgenome.org/nomenclature-conventions). In bacteria, gene symbols are all in lowercase letters and italicized, protein names are nonitalic with only the first letter in uppercase.7 Ang-(1–7) indicates angiotensin (1–7); GPCR, G-protein–coupled receptor; HGNC, HUGO Gene Nomenclature Committee; ID, identifier; MGI, Mouse Genome Informatics; NCBI, National Center for Biotechnology Information; and SGD, Saccharomyces Genome Database.The duplication in nomenclature (Table) has unfortunately resulted in some misunderstandings and confusion in the Ang field because there are some papers that attribute Ang-(1–7) effects to yeast Mas1 protein.8–11 This may be especially important in the context of interpretation of results and consideration of tools used to interrogate mammalian MAS because it is likely that in some studies, antibodies to the yeast Mas1 protein rather than to the GPCR MAS may have been used erroneously. To further add to the complexity, the molecular size of the yeast Mas1 protein (~50 kDa) is not that dissimilar to that of human MAS (~40 kDa), and antibodies against MAS, which we tested, were nonspecific.12 The confusion was additionally increased in 2016, when a putative thermostable lipase from a marine Streptomyces species was also named Mas1 (Table).13 However, at least until now, this protein has not been confused with MAS.The aim of this brief review is to highlight the importance of discriminating between the different Mas1 proteins and to ensure that the GPCR MAS is indeed the protein of interest when examining Ang-(1–7) (patho)physiological actions. Here, we provide a historical overview of MAS and describe the origin of the name and how its functions have been unraveled.Discovery of MAS as a Proto-OncogeneThe MAS gene was first identified in 1986 using an assay for human oncogenes based on their ability to induce tumorigenicity of NIH 3T3 cells in nude mice.14,15 Briefly, NIH 3T3 cells were cotransfected with DNA purified from a human tumor along with a G418 selectable marker. After selection and growth in culture, the G418-resistant cells were injected into nude mice. Several weeks later, DNA from tumors that formed in the mice was purified. The human DNA isolated from one of these tumors contained the MAS gene. The name MAS is an abbreviation of the last name (Massey) of the person who donated the human tumor from which the MAS gene was derived. This gene was cloned and shown to possess the ability to induce NIH 3T3 cells to form foci of transformed cells in culture and to form tumors in nude mice.4 Therefore, MAS was called a proto-oncogene. However, MAS likely did not contribute to the formation of the human tumor because the gene did not appear to be rearranged or mutated in the original human tumor DNA; rather, the transforming potential of MAS in NIH 3T3 cells seemed to be activated by DNA rearrangement or amplification during transfection into NIH 3T3 cells.4,16 Moreover, recent findings have suggested that MAS activation by Ang-(1–7) could actually be a therapeutic target against tumors and has been suggested as a putative anticancer treatment.17MAS as an Ang II ReceptorAlready at the time of its discovery, the DNA sequence of the MAS gene was determined and shown to encode a protein with a 7-transmembrane domain structure similar to that of GPCR.4 Despite the fact that only 1 protein is encoded by the gene, we recently demonstrated that the mouse Mas gene with 4 promoters and 12 exons generates at least 12 different mRNAs by alternative splicing at the 5′ untranslated region and is thereby the most complex gene of all GPCRs.18 To define its ligand, Jackson et al19 expressed MAS in Xenopus oocytes and in a mammalian cell line. Oocytes exhibited a dose-dependent induction of an inward current in response to Ang I, II, and III, and in transfected cells, Ang II and III led to intracellular Ca2+ release and to the initiation of DNA synthesis. Based on these results, MAS was suggested to be a functional Ang II receptor. However, whereas several follow-up studies supported this assumption,20–23 Ambroz et al24 showed that the Ca2+ release after Ang II treatment was only observed in MAS-transfected cells additionally expressing endogenous Ang II receptors. Cloning of the real Ang II receptor, AT1, in 199125,26 and the discovery of a direct interaction between MAS and AT1 in 200527,28 partly explained the original observations of Jackson et al19 in Xenopus oocytes and revealed that MAS is not an Ang II receptor per se but modulates AT1 signaling.Mas as an Imprinted GeneIn 1994, Mas was reported to be maternally imprinted in mice29 and in human breast tissue,30 that is, 1 of the 2 parental Mas alleles was epigenetically silenced. The Mas gene is located in close proximity to the imprinted Igf2r gene in the human and mouse genomes.31,32 Imprinting of this chromosomal area is regulated by an intronic control element starting the transcription of the long noncoding RNA, Airn (Antisense Igf2r RNA noncoding). The transcribed antisense RNA overlaps (and silences) the Igf2r promoter and partially the Mas gene.33,34 Using Mas-deficient mice,35 we could show that Mas is biallelically expressed.36 Because Villar and Pedersen29 and Miller et al30 used reverse-transcription–polymerase-chain reaction assays that lack strand selectivity to discover imprinting of Mas, it is very likely that they detected Airn as maternally imprinted RNA and not the Mas transcript. Thus, Airn but not Mas is monoallelically expressed in mouse and man.MAS as an Ang-(1–7) ReceptorThe first evidence for a receptor for Ang-(1–7) distinct from the Ang II receptors came from the observation that Ang-(1–7) was equipotent to Ang II for vasopressin release from hypothalamus-neurohypophyseal explants37 but in contrast to Ang II had no effect on drinking behavior.38 Moreover, Ang-(1–7) was reported to exert vasodilatory effects by releasing NO resulting in a blood pressure decrease.39 This and other actions of Ang-(1–7), which all opposed the effects of Ang II, further supported that Ang-(1–7) mediates its effects through a novel non-AT1/AT2 receptor subtype. The final proof for the existence of a specific receptor for the peptide was the discovery of a selective antagonist for Ang-(1–7) in 1994.40,41Yet, it was only in 2003 that more definitive evidence for a specific binding site for Ang-(1–7) was demonstrated with the finding that MAS is a receptor for the heptapeptide.42 In that study, specific binding of 125I-Ang-(1–7) to Mas-transfected cells was reported. Moreover, the specific binding of 125I-Ang-(1–7) but not of 125I-Ang II or 125I-Ang IV to kidney sections was abolished by genetic deletion of Mas. In addition, Mas-deficient mice completely lack the antidiuretic action of Ang-(1–7) after an acute water load and Mas-deficient aortas lost their Ang-(1–7)–induced relaxation response. These findings provided the first clear molecular basis for the physiological actions of this biologically active peptide. At this point, an orphan receptor met an orphan peptide filling an important gap in our understanding of the renin-Ang system. Further support for these findings was obtained in different laboratories. In 2005, Tallant et al43 showed that transfection of cultured myocytes with an antisense oligonucleotide to Mas blocked the Ang-(1–7)–mediated inhibition of serum-stimulated MAPK (mitogen-activated protein kinase) activation, whereas a sense oligonucleotide was ineffective. Ang-(1–7) was found to stimulate NO release and eNOS (endothelial NO synthase) activation in endothelial cells, and these effects were blocked by the specific MAS antagonist, A-779.44,45 In addition, Mas deficiency abolishes all the known cardiovascular effects of Ang-(1–7).46 Indeed, in most instances, genetic deletion of Mas causes alterations opposed to those produced by treatment with Ang-(1–7).Nevertheless, there are recent reports that Ang-(1–7) has no effect on MAS-transfected cells but exerts biased agonism or even antagonism at the AT1 receptor.47–49 Moreover, using other MAS agonists (neuropeptide FF and AR234960) and inverse agonists (AR244555), biased signaling of MAS itself was described.50 Heteromeric interactions of MAS with AT1, AT2, bradykinin B2, and endothelin B receptors further complicate this issue.27,28,51–53 Therefore, future studies need to clarify the relationship between MAS and Ang-(1–7), which may depend on the specific cell types and their expression of other GPCRs.54ConclusionsIn conclusion, this brief review highlights important points related to some misconceptions and confusions on the nomenclature of MAS and its functions (Table), especially in the context of cardiovascular pathophysiology. We suggest that the original name, Mas, is used for the GPCR.Important Take Home MessagesThe MAS1 gene in yeast codes for Mas1p (mitochondrial assembly protein 1)—a protease essential for protein import into mitochondria and homologous to the human PMPCB gene.MAS1 or MAS in tetrapods is a GPCR for Ang-(1–7) but not for Ang II.Yeast Mas1 protein has a molecular size of 50 to 52 kDa, whereas mammalian MAS has a molecular size of 37 to 40 kDa.When probing for MAS1 or MAS in the context of Ang-(1–7) biology, ensure the correct primers and antibodies are used to assess expression of mRNA and protein, respectively. It should be noted though that currently the authors are unaware of commercially available antibodies that specifically detect MAS at physiological expression levels. However, we demonstrated that the following primer pair is suitable to quantify human MAS mRNA by quantitative polymerase chain reaction and may also be used in mice: 5′-GCTACAACACGGGCCTCTATCTG-3′; 5′-TACTCCATGGTGGTCACCAAGC-3′; fragment length, 160 bp.The mouse Mas gene is not imprinted.The MAS gene is a proto-oncogene but has not yet been shown to cause a human tumor.Ang-(1–7)/MAS mediates effects that oppose actions of Ang II/AT1.MAS interacts with other GPCRs.Sources of FundingR.M. Touyz is funded through a British Heart Foundation chair and grant (RG/13/7/30099 and RE/13/5/30177).DisclosuresNone.FootnotesThis article was sent to Robert M. Carey, Consulting Editor, for review by expert referees, editorial decision, and final disposition.Correspondence to Rhian M. Touyz, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Pl, Glasgow G12 8TA, United Kingdom. Email rhian.[email protected]ac.ukReferences1. Yaffe MP, Schatz G. Two nuclear mutations that block mitochondrial protein import in yeast.Proc Natl Acad Sci USA. 1984; 81:4819–4823.CrossrefMedlineGoogle Scholar2. Witte C, Jensen RE, Yaffe MP, Schatz G. MAS1, a gene essential for yeast mitochondrial assembly, encodes a subunit of the mitochondrial processing protease.EMBO J. 1988; 7:1439–1447.CrossrefMedlineGoogle Scholar3. Poveda-Huertes D, Mulica P, Vögtle FN. The versatility of the mitochondrial presequence processing machinery: cleavage, quality control and turnover.Cell Tissue Res. 2017; 367:73–81. doi: 10.1007/s00441-016-2492-9CrossrefMedlineGoogle Scholar4. Young D, Waitches G, Birchmeier C, Fasano O, Wigler M. Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains.Cell. 1986; 45:711–719.CrossrefMedlineGoogle Scholar5. Bader M, Alenina N, Andrade-Navarro MA, Santos RA. MAS and its related G protein-coupled receptors, Mrgprs.Pharmacol Rev. 2014; 66:1080–1105. doi: 10.1124/pr.113.008136CrossrefMedlineGoogle Scholar6. Solinski HJ, Gudermann T, Breit A. Pharmacology and signaling of MAS-related G protein-coupled receptors.Pharmacol Rev. 2014; 66:570–597. doi: 10.1124/pr.113.008425CrossrefMedlineGoogle Scholar7. Demerec M, Adelberg EA, Clark AJ, Hartman PE. A proposal for a uniform nomenclature in bacterial genetics.Genetics. 1966; 54:61–76.CrossrefMedlineGoogle Scholar8. Ager EI, Neo J, Christophi C. The renin-angiotensin system and malignancy.Carcinogenesis. 2008; 29:1675–1684. doi: 10.1093/carcin/bgn171CrossrefMedlineGoogle Scholar9. Xu J, Fan J, Wu F, Huang Q, Guo M, Lv Z, Han J, Duan L, Hu G, Chen L, Liao T, Ma W, Tao X, Jin Y. The ACE2/angiotensin-(1-7)/Mas receptor axis: pleiotropic roles in cancer.Front Physiol. 2017; 8:276. doi: 10.3389/fphys.2017.00276CrossrefMedlineGoogle Scholar10. Touyz RM, Montezano AC. Angiotensin-(1-7) and vascular function: the clinical context.Hypertension. 2018; 71:68–69. doi: 10.1161/HYPERTENSIONAHA.117.10406LinkGoogle Scholar11. Su YY, Chen CH, Chien CY, Lin WC, Huang WT, Li SH. Mitochondrial assembly receptor expression is an independent prognosticator for patients with oral tongue squamous cell carcinoma.J Renin Angiotensin Aldosterone Syst. 2017; 18:1470320317717904. doi: 10.1177/1470320317717904CrossrefGoogle Scholar12. Burghi V, Fernández NC, Gándola YB, Piazza VG, Quiroga DT, Guilhen Mario É, Felix Braga J, Bader M, Santos RAS, Dominici FP, Muñoz MC. Validation of commercial Mas receptor antibodies for utilization in Western Blotting, immunofluorescence and immunohistochemistry studies.PLoS One. 2017; 12:e0183278. doi: 10.1371/journal.pone.0183278CrossrefMedlineGoogle Scholar13. Yuan D, Lan D, Xin R, Yang B, Wang Y. Screening and characterization of a thermostable lipase from marine Streptomyces sp. strain W007.Biotechnol Appl Biochem. 2016; 63:41–50. doi: 10.1002/bab.1338CrossrefMedlineGoogle Scholar14. Birchmeier C, Birnbaum D, Waitches G, Fasano O, Wigler M. Characterization of an activated human ros gene.Mol Cell Biol. 1986; 6:3109–3116.CrossrefMedlineGoogle Scholar15. Fasano O, Birnbaum D, Edlund L, Fogh J, Wigler M. New human transforming genes detected by a tumorigenicity assay.Mol Cell Biol. 1984; 4:1695–1705.CrossrefMedlineGoogle Scholar16. Rabin M, Birnbaum D, Young D, Birchmeier C, Wigler M, Ruddle FH. Human ros1 and mas1 oncogenes located in regions of chromosome 6 associated with tumor-specific rearrangements.Oncogene Res. 1987; 1:169–178.MedlineGoogle Scholar17. Gallagher PE, Arter AL, Deng G, Tallant EA. Angiotensin-(1-7): a peptide hormone with anti-cancer activity.Curr Med Chem. 2014; 21:2417–2423.CrossrefMedlineGoogle Scholar18. Alenina N, Böhme I, Bader M, Walther T. Multiple non-coding exons and alternative splicing in the mouse Mas protooncogene.Gene. 2015; 568:155–164. doi: 10.1016/j.gene.2015.05.043CrossrefMedlineGoogle Scholar19. Jackson TR, Blair LA, Marshall J, Goedert M, Hanley MR. The mas oncogene encodes an angiotensin receptor.Nature. 1988; 335:437–440. doi: 10.1038/335437a0CrossrefMedlineGoogle Scholar20. Andrawis NS, Dzau VJ, Pratt RE. Autocrine stimulation of mas oncogene leads to altered growth control.Cell Biol Int Rep. 1992; 16:547–556.CrossrefMedlineGoogle Scholar21. Jackson TR, Hanley MR. Tumor promoter 12-O-tetradecanoylphorbol 13-acetate inhibits mas/angiotensin receptor-stimulated inositol phosphate production and intracellular Ca2+ elevation in the 401L-C3 neuronal cell line.FEBS Lett. 1989; 251:27–30.CrossrefMedlineGoogle Scholar22. McGillis JP, Sudduth-Klinger J, Harrowe G, Mitsuhashi M, Payan DG. Transient expression of the angiotensin II receptor: a rapid and functional analysis of a calcium-mobilizing seven-transmembrane domain receptor in COS-7 cells.Biochem Biophys Res Commun. 1989; 165:935–941.CrossrefMedlineGoogle Scholar23. Poyner DR, Hawkins PT, Benton HP, Hanley MR. Changes in inositol lipids and phosphates after stimulation of the MAS-transfected NG115-401L-C3 cell line by mitogenic and non-mitogenic stimuli.Biochem J. 1990; 271:605–611.CrossrefMedlineGoogle Scholar24. Ambroz C, Clark AJ, Catt KJ. The mas oncogene enhances angiotensin-induced [Ca2+]i responses in cells with pre-existing angiotensin II receptors.Biochim Biophys Acta. 1991; 1133:107–111.CrossrefMedlineGoogle Scholar25. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor.Nature. 1991; 351:233–236. doi: 10.1038/351233a0CrossrefMedlineGoogle Scholar26. Sasaki K, Yamano Y, Bardhan S, Iwai N, Murray JJ, Hasegawa M, Matsuda Y, Inagami T. Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor.Nature. 1991; 351:230–233. doi: 10.1038/351230a0CrossrefMedlineGoogle Scholar27. Kostenis E, Milligan G, Christopoulos A, Sanchez-Ferrer CF, Heringer-Walther S, Sexton PM, Gembardt F, Kellett E, Martini L, Vanderheyden P, Schultheiss HP, Walther T. G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor.Circulation. 2005; 111:1806–1813. doi: 10.1161/01.CIR.0000160867.23556.7DLinkGoogle Scholar28. Santos EL, Reis RI, Silva RG, Shimuta SI, Pecher C, Bascands JL, Schanstra JP, Oliveira L, Bader M, Paiva AC, Costa-Neto CM, Pesquero JB. Functional rescue of a defective angiotensin II AT1 receptor mutant by the Mas protooncogene.Regul Pept. 2007; 141:159–167. doi: 10.1016/j.regpep.2006.12.030CrossrefMedlineGoogle Scholar29. Villar AJ, Pedersen RA. Parental imprinting of the Mas protooncogene in mouse.Nat Genet. 1994; 8:373–379. doi: 10.1038/ng1294-373CrossrefMedlineGoogle Scholar30. Miller N, McCann AH, O'Connell D, Pedersen IS, Spiers V, Gorey T, Dervan PA. The MAS proto-oncogene is imprinted in human breast tissue.Genomics. 1997; 46:509–512. doi: 10.1006/geno.1997.5063CrossrefMedlineGoogle Scholar31. Barlow DP, Stöger R, Herrmann BG, Saito K, Schweifer N. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus.Nature. 1991; 349:84–87. doi: 10.1038/349084a0CrossrefMedlineGoogle Scholar32. Schweifer N, Valk PJ, Delwel R, Cox R, Francis F, Meier-Ewert S, Lehrach H, Barlow DP. Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene.Genomics. 1997; 43:285–297. doi: 10.1006/geno.1997.4816CrossrefMedlineGoogle Scholar33. Lyle R, Watanabe D, te Vruchte D, Lerchner W, Smrzka OW, Wutz A, Schageman J, Hahner L, Davies C, Barlow DP. The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas1.Nat Genet. 2000; 25:19–21. doi: 10.1038/75546CrossrefMedlineGoogle Scholar34. Wutz A, Smrzka OW, Schweifer N, Schellander K, Wagner EF, Barlow DP. Imprinted expression of the Igf2r gene depends on an intronic CpG island.Nature. 1997; 389:745–749. doi: 10.1038/39631CrossrefMedlineGoogle Scholar35. Walther T, Balschun D, Voigt JP, Fink H, Zuschratter W, Birchmeier C, Ganten D, Bader M. Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene.J Biol Chem. 1998; 273:11867–11873.CrossrefMedlineGoogle Scholar36. Alenina N, Bader M, Walther T. Imprinting of the murine MAS protooncogene is restricted to its antisense RNA.Biochem Biophys Res Commun. 2002; 290:1072–1078. doi: 10.1006/bbrc.2001.6328CrossrefMedlineGoogle Scholar37. Schiavone MT, Santos RA, Brosnihan KB, Khosla MC, Ferrario CM. Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide.Proc Natl Acad Sci USA. 1988; 85:4095–4098.CrossrefMedlineGoogle Scholar38. Fitzsimons JT. The effect on drinking of peptide precursors and of shorter chain peptide fragments of angiotensin II injected into the rat's diencephalon.J Physiol. 1971; 214:295–303.CrossrefMedlineGoogle Scholar39. Santos RA, Campagnole-Santos MJ, Andrade SP. Angiotensin-(1-7): an update.Regul Pept. 2000; 91:45–62.CrossrefMedlineGoogle Scholar40. Santos RA, Campagnole-Santos MJ, Baracho NC, Fontes MA, Silva LC, Neves LA, Oliveira DR, Caligiorne SM, Rodrigues AR, Gropen Júnior C. Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors.Brain Res Bull. 1994; 35:293–298.CrossrefMedlineGoogle Scholar41. Ambühl P, Felix D, Khosla MC. [7-D-ALA]-angiotensin-(1-7): selective antagonism of angiotensin-(1-7) in the rat paraventricular nucleus.Brain Res Bull. 1994; 35:289–291.CrossrefMedlineGoogle Scholar42. Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas.Proc Natl Acad Sci USA. 2003; 100:8258–8263. doi: 10.1073/pnas.1432869100CrossrefMedlineGoogle Scholar43. Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor.Am J Physiol Heart Circ Physiol. 2005; 289:H1560–H1566. doi: 10.1152/ajpheart.00941.2004CrossrefMedlineGoogle Scholar44. Sampaio WO, Souza dos Santos RA, Faria-Silva R, da Mata Machado LT, Schiffrin EL, Touyz RM. Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways.Hypertension. 2007; 49:185–192. doi: 10.1161/01.HYP.0000251865.35728.2fLinkGoogle Scholar45. Wiemer G, Dobrucki LW, Louka FR, Malinski T, Heitsch H. AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium.Hypertension. 2002; 40:847–852.LinkGoogle Scholar46. Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, Campagnole-Santos MJ. The ACE2/angiotensin-(1-7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1-7).Physiol Rev. 2018; 98:505–553. doi: 10.1152/physrev.00023.2016CrossrefMedlineGoogle Scholar47. Galandrin S, Denis C, Boularan C, Marie J, M'Kadmi C, Pilette C, Dubroca C, Nicaise Y, Seguelas MH, N'Guyen D, Banères JL, Pathak A, Sénard JM, Galés C. Cardioprotective angiotensin-(1-7) peptide acts as a natural-biased ligand at the angiotensin II type 1 receptor.Hypertension. 2016; 68:1365–1374. doi: 10.1161/HYPERTENSIONAHA.116.08118LinkGoogle Scholar48. Teixeira LB, Parreiras-E-Silva LT, Bruder-Nascimento T, Duarte DA, Simões SC, Costa RM, Rodríguez DY, Ferreira PAB, Silva CAA, Abrao EP, Oliveira EB, Bouvier M, Tostes RC, Costa-Neto CM. Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy.Sci Rep. 2017; 7:11903. doi: 10.1038/s41598-017-12074-3CrossrefMedlineGoogle Scholar49. Gaidarov I, Adams J, Frazer J, Anthony T, Chen X, Gatlin J, Semple G, Unett DJ. Angiotensin (1-7) does not interact directly with MAS1, but can potently antagonize signaling from the AT1 receptor.Cell Signal. 2018; 50:9–24. doi: 10.1016/j.cellsig.2018.06.007CrossrefMedlineGoogle Scholar50. Tirupula KC, Desnoyer R, Speth RC, Karnik SS. Atypical signaling and functional desensitization response of MAS receptor to peptide ligands.PLoS One. 2014; 9:e103520. doi: 10.1371/journal.pone.0103520CrossrefMedlineGoogle Scholar51. Leonhardt J, Villela DC, Teichmann A, et al. Evidence for heterodimerization and functional interaction of the angiotensin type 2 receptor and the receptor MAS.Hypertension. 2017; 69:1128–1135. doi: 10.1161/HYPERTENSIONAHA.116.08814LinkGoogle Scholar52. Cerrato BD, Carretero OA, Janic B, Grecco HE, Gironacci MM. Heteromerization between the bradykinin B2 receptor and the angiotensin-(1-7) Mas receptor: functional consequences.Hypertension. 2016; 68:1039–1048. doi: 10.1161/HYPERTENSIONAHA.116.07874LinkGoogle Scholar53. Hood KY, Yusuf H, Findlay JE, Castro CH, Baillie GS, Montezano AC, MacLean MR, Touyz RM. ANG-(1–7) and ET-1, a new partnership.J Hypertens. 2016; 34:e382.CrossrefGoogle Scholar54. Karnik SS, Singh KD, Tirupula K, Unal H. Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR review 22.Br J Pharmacol. 2017; 174:737–753. doi: 10.1111/bph.13742CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Miller A and Arnold A (2022) The renin-angiotensin system and cardiovascular autonomic control in aging, Peptides, 10.1016/j.peptides.2021.170733, 150, (170733), Online publication date: 1-Apr-2022. Zhang Q, Chen F, Wang F, Di X, Li W and Zhang H (2022) A Novel Modulator of the Renin–Angiotensin System, Benzoylaconitine, Attenuates Hypertension by Targeting ACE/ACE2 in Enhancing Vasodilation and Alleviating Vascular Inflammation, Frontiers in Pharmacology, 10.3389/fphar.2022.841435, 13 Sahu S, Patil C, Kumar S, Apparsundaram S and Goyal R (2021) Role of ACE2-Ang (1–7)-Mas axis in post-COVID-19 complications and its dietary modulation, Molecular and Cellular Biochemistry, 10.1007/s11010-021-04275-2, 477:1, (225-240), Online publication date: 1-Jan-2022. Gersh F, O'Keefe J, Lavie C and Henry B (2021) The Renin-Angiotensin-Aldosterone System in Postmenopausal Women: The Promise of Hormone Therapy, Mayo Clinic Proceedings, 10.1016/j.mayocp.2021.08.009, 96:12, (3130-3141), Online publication date: 1-Dec-2021. Cumpstey A, Clark A, Santolini J, Jackson A and Feelisch M (2021) COVID-19: A Redox Disease—What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment, Antioxidants & Redox Signaling, 10.1089/ars.2021.0017, 35:14, (1226-1268), Online publication date: 10-Nov-2021. Marins F, Oliveira A, Qadri F, Motta-Santos D, Alenina N, Bader M, Fontes M and Santos R (2021) Alamandine but not angiotensin-(1–7) produces cardiovascular effects at the rostral insular cortex, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 10.1152/ajpregu.00308.2020, 321:3, (R513-R52
Referência(s)