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Gene Review

APLN  -  apelin

Homo sapiens

Synonyms: APEL, APJ endogenous ligand, Apelin, XNPEP2
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Disease relevance of APLN

  • These studies demonstrate the ability of a small peptide ligand to block the function of APJ as an HIV-1 coreceptor, identify apelin sequences important for the inhibition, and provide new reagents for the investigation of the significance of APJ to HIV-1 infection and pathogenesis [1].
  • Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry [1].
  • We additionally extend the clinical significance of this work by reporting for the first time circulating human apelin levels and demonstrating increases in the plasma level of apelin in patients with left ventricular dysfunction [2].
  • Apelin, a newly identified adipokine up-regulated by insulin and obesity [3].
  • As assessed by quantitative RT-PCR analysis, left ventricular apelin mRNA levels were increased 4.7-fold in chronic heart failure (CHF) due to coronary heart disease (p<0.01) and 3.3-fold due to idiopathic dilated cardiomyopathy (p<0.05), whereas atrial apelin mRNA levels were unchanged [4].

Psychiatry related information on APLN

  • Intraperitoneal apelin injections induced an increase in drinking behavior within the first 30 min after injection, with a return to baseline within 1 h [5].
  • Hypothesis-testing abilities were assessed using a modification of the discrimination-learning paradigm employed by Nelson, Kamhi, and Apel (1987) that was designed to minimize the short-term memory demands of the task [6].

High impact information on APLN


Chemical compound and disease context of APLN


Biological context of APLN

  • Suppression of APJ with small-interfering RNA (siRNA) abolished the apelin-induced cell proliferation [10].
  • Synthetic peptides derived from the C-terminal amino acid sequence of bovine preproapelin were capable of specifically promoting the acidification rate in the cells expressing the APJ receptor in a range from 10(-7) to 10(-10) M, indicating that apelin is an endogenous ligand for the APJ receptor [11].
  • Apelin suppresses apoptosis of human osteoblasts [12].
  • Together, our findings show that USF exerts a stimulatory role in regulation of breast apelin expression during pregnancy and lactation [13].
  • Mutagenesis and overexpression assays showed that USF up-regulates basal and inducible apelin transcription [13].

Anatomical context of APLN


Associations of APLN with chemical compounds

  • Antiviral potency was influenced by the integrity of methionine 75, which contributes to APJ-binding affinity, and by the retention of apelin residues 63 to 65 [1].
  • In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C-terminal apelin peptide, apelin-13, resulted in significant changes in pharmacology [16].
  • Furthermore, LY294002 (PI3 kinase inhibitor) blocked the activation of Akt by apelin and abolished the apelin-induced cell proliferation [10].
  • Furthermore, apelin protects against apoptosis induced by the glucocorticoid dexamethasone [12].
  • Both sequence and mRNA expression distribution analyses revealed similarities between apelin and angiotensin II, suggesting they that share related physiological roles [5].

Physical interactions of APLN

  • CONCLUSIONS: Our findings of a significantly reduced peripheral level of apelin coupled with elevated AVP point to a subtle but definite vasopressinergic dysfunction in autism that could play a role in the etiopathophysiology of this disorder in humans [17].
  • Among these, we identified genes and pathways already associated with renal dysfunction as well as a new subset of genes previously unknown to participate in this complication, including a G protein-coupled receptor that binds apelin, a protein phosphatase (calcineurin B) and a number of neuropeptide receptors and growth factors [18].

Regulatory relationships of APLN


Other interactions of APLN

  • The restricted presence of apelin-LI in endothelial cells suggests that endothelial apelin may play a role as a locally secreted cardiovascular mediator acting on APJ receptors present on the vascular smooth muscle and on cardiac myocytes to regulate vascular tone and cardiac contractility [14].
  • Analysis of apelin analogues demonstrated that potent and specific antiviral activity was retained by a 13-residue, arginine-rich peptide [1].
  • Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors [21].
  • In response to agonist ligands both the orexin-1 and apelin receptors were able to rapidly translocate both beta-arrestin 1-GFP and beta-arrestin 2-GFP from cytoplasm to the plasma membrane [22].
  • Taken together, these data outline the potential role of apelin as an autocrine/paracrine-acting peptide on ACTH release and provide morphological and neuroendocrine basis for further studies that explore the physiological role of apelin in the regulation of anterior pituitary functions [23].

Analytical, diagnostic and therapeutic context of APLN


  1. Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. Cayabyab, M., Hinuma, S., Farzan, M., Choe, H., Fukusumi, S., Kitada, C., Nishizawa, N., Hosoya, M., Nishimura, O., Messele, T., Pollakis, G., Goudsmit, J., Fujino, M., Sodroski, J. J. Virol. (2000) [Pubmed]
  2. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Chen, M.M., Ashley, E.A., Deng, D.X., Tsalenko, A., Deng, A., Tabibiazar, R., Ben-Dor, A., Fenster, B., Yang, E., King, J.Y., Fowler, M., Robbins, R., Johnson, F.L., Bruhn, L., McDonagh, T., Dargie, H., Yakhini, Z., Tsao, P.S., Quertermous, T. Circulation (2003) [Pubmed]
  3. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Boucher, J., Masri, B., Daviaud, D., Gesta, S., Guigné, C., Mazzucotelli, A., Castan-Laurell, I., Tack, I., Knibiehler, B., Carpéné, C., Audigier, Y., Saulnier-Blache, J.S., Valet, P. Endocrinology (2005) [Pubmed]
  4. Circulating and cardiac levels of apelin, the novel ligand of the orphan receptor APJ, in patients with heart failure. Földes, G., Horkay, F., Szokodi, I., Vuolteenaho, O., Ilves, M., Lindstedt, K.A., Mäyränpää, M., Sármán, B., Seres, L., Skoumal, R., Lakó-Futó, Z., deChâtel, R., Ruskoaho, H., Tóth, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  5. Characterization of apelin, the ligand for the APJ receptor. Lee, D.K., Cheng, R., Nguyen, T., Fan, T., Kariyawasam, A.P., Liu, Y., Osmond, D.H., George, S.R., O'Dowd, B.F. J. Neurochem. (2000) [Pubmed]
  6. Hypothesis-testing abilities of language-impaired children. Weismer, S.E. Journal of speech and hearing research. (1991) [Pubmed]
  7. Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity. Lee, D.K., George, S.R., O'dowd, B.F. Trends Pharmacol. Sci. (2006) [Pubmed]
  8. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. De Mota, N., Reaux-Le Goazigo, A., El Messari, S., Chartrel, N., Roesch, D., Dujardin, C., Kordon, C., Vaudry, H., Moos, F., Llorens-Cortes, C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  9. Distribution of apelin-synthesizing neurons in the adult rat brain. Reaux, A., Gallatz, K., Palkovits, M., Llorens-Cortes, C. Neuroscience (2002) [Pubmed]
  10. Apelin and its receptor are expressed in human osteoblasts. Xie, H., Tang, S.Y., Cui, R.R., Huang, J., Ren, X.H., Yuan, L.Q., Lu, Y., Yang, M., Zhou, H.D., Wu, X.P., Luo, X.H., Liao, E.Y. Regul. Pept. (2006) [Pubmed]
  11. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Tatemoto, K., Hosoya, M., Habata, Y., Fujii, R., Kakegawa, T., Zou, M.X., Kawamata, Y., Fukusumi, S., Hinuma, S., Kitada, C., Kurokawa, T., Onda, H., Fujino, M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  12. Apelin suppresses apoptosis of human osteoblasts. Xie, H., Yuan, L.Q., Luo, X.H., Huang, J., Cui, R.R., Guo, L.J., Zhou, H.D., Wu, X.P., Liao, E.Y. Apoptosis (2007) [Pubmed]
  13. Characterization of the 5'-regulatory regions of the rat and human apelin genes and regulation of breast apelin by USF. Wang, G., Qi, X., Wei, W., Englander, E.W., Greeley, G.H. FASEB J. (2006) [Pubmed]
  14. Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Kleinz, M.J., Davenport, A.P. Regul. Pept. (2004) [Pubmed]
  15. Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells. Kleinz, M.J., Skepper, J.N., Davenport, A.P. Regul. Pept. (2005) [Pubmed]
  16. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. Medhurst, A.D., Jennings, C.A., Robbins, M.J., Davis, R.P., Ellis, C., Winborn, K.Y., Lawrie, K.W., Hervieu, G., Riley, G., Bolaky, J.E., Herrity, N.C., Murdock, P., Darker, J.G. J. Neurochem. (2003) [Pubmed]
  17. Reduced plasma apelin levels in patients with autistic spectrum disorder. Boso, M., Emanuele, E., Politi, P., Pace, A., Arra, M., Ucelli di Nemi, S., Barale, F. Arch. Med. Res. (2007) [Pubmed]
  18. Gene expression profiling of renal dysfunction in rats with experimental cirrhosis. López-Parra, M., Telleria, N., Titos, E., Planagumà, A., González-Périz, A., Arroyo, V., Rodés, J., Clària, J. J. Hepatol. (2006) [Pubmed]
  19. Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells. Masri, B., Morin, N., Cornu, M., Knibiehler, B., Audigier, Y. FASEB J. (2004) [Pubmed]
  20. Therapeutic potential of interfering with apelin signalling. Sorli, S.C., van den Berghe, L., Masri, B., Knibiehler, B., Audigier, Y. Drug Discov. Today (2006) [Pubmed]
  21. Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors. Lee, D.K., Lança, A.J., Cheng, R., Nguyen, T., Ji, X.D., Gobeil, F., Chemtob, S., George, S.R., O'Dowd, B.F. J. Biol. Chem. (2004) [Pubmed]
  22. Visualizing differences in ligand-induced beta-arrestin-GFP interactions and trafficking between three recently characterized G protein-coupled receptors. Evans, N.A., Groarke, D.A., Warrack, J., Greenwood, C.J., Dodgson, K., Milligan, G., Wilson, S. J. Neurochem. (2001) [Pubmed]
  23. Cellular localization of apelin and its receptor in the anterior pituitary: evidence for a direct stimulatory action of apelin on ACTH release. Reaux-Le Goazigo, A., Alvear-Perez, R., Zizzari, P., Epelbaum, J., Bluet-Pajot, M.T., Llorens-Cortes, C. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  24. Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K., Kasuya, Y., Mochizuki, N., Fukamizu, A. J. Biol. Chem. (2004) [Pubmed]
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