[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/apelin-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki24\/apelin-wikipedia\/","headline":"Apelin – Wikipedia","name":"Apelin – Wikipedia","description":"before-content-x4 Mammalian protein found in Homo sapiens after-content-x4 Apelin (also known as APLN) is a peptide that in humans is","datePublished":"2015-02-21","dateModified":"2015-02-21","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":100,"height":100},"url":"https:\/\/wiki.edu.vn\/en\/wiki24\/apelin-wikipedia\/","wordCount":14598,"articleBody":"     (adsbygoogle = window.adsbygoogle || []).push({});before-content-x4Mammalian protein found in Homo sapiens       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene.[5] Apelin is one of two endogenous ligands for the G-protein-coupled APJ receptor[6][7][8][9][10] that is expressed at the surface of some cell types.[11] It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.Table of Contents       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Discovery[edit]Biosynthesis[edit]Physiological functions[edit]Vascular[edit]Cardiac[edit]Exercise[edit]Brain[edit]Adipose tissue[edit]Digestive[edit]Bone[edit]Muscle aging[edit]References[edit]Further reading[edit]External links[edit]Discovery[edit]Apelin is a peptide hormone that was identified in 1998 by Masahiko Fujino and his colleagues at Gunma University and Takeda Pharmaceutical Company.[5] In 2013, a second peptide hormone named Elabela was found by Bruno Reversade to also act as an endogenous ligand to the APLNR.Biosynthesis[edit]The apelin gene encodes a pre-proprotein of 77 amino acids,[5] with a signal peptide in the N-terminal region. After translocation into the endoplasmic reticulum and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and\/or the concentrations of those peptides in human plasma has been questioned.[12] Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.[13]Physiological functions[edit]The sites of receptor expression are linked to the different functions played by apelin in the organism.Vascular[edit]Vascular expression of the receptor[14][15] participates in the control of blood pressure[6] and its activation promotes the formation of new blood vessels (angiogenesis).[15][16][17][18] The blood pressure-lowering (hypotensive) effect of apelin results from the activation of receptors expressed at the surface of endothelial cells.[14][15] This activation induces the release of nitric oxide (NO),[19] a potent vasodilator, which induces relaxation of the smooth muscle cells of artery wall. Studies performed on mice  knocked out for the apelin receptor gene[20] have suggested the existence of a balance between angiotensin II signalling (which increases blood pressure)e and apelin signalling (which lowers it).  The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates signal transduction cascades inside the cell, including extracellular signal-regulated kinases (ERKs), protein kinase B (PKB, also known as Akt), and p70 s6 kinase phosphorylation,[16][21] which lead to the proliferation of endothelial cells and the formation of new blood vessels.[17]Genetic knockout of the apelin gene is associated with a delay in the development of the retinal vasculature.[22]       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Cardiac[edit]The apelin receptor is expressed early during the embryonic development of the heart, where it regulates the migration of cell progenitors fated to differentiate into cardiomyocytes,  the contractile cells of the heart.[23][24] Its expression is also detected in the cardiomyocytes of the adult where apelin behaves as one of the most potent stimulator of cardiac contractility.[7][25][26] Aged apelin knockout mice develop progressive impairment of cardiac contractility.[27]  Apelin acts as a mediator of the cardiovascular control, including for blood pressure and blood flow. It is one of the most potent stimulators of cardiac contractility yet identified, and plays a role in cardiac tissue remodeling. Apelin levels are increased in left ventricles of patients with chronic heart failure and also in patients with chronic liver disease.[28]Exercise[edit]The plasma concentration of apelin is shown to increase during exercise.[29] Paradoxically, exogenous apelin in healthy volunteers reduced VO2 peak (peak oxygen consumption) in an endurance test.[30]Brain[edit]Apelin receptor is also expressed in the neurons of brain areas involved in regulating water and food intake.[6][31][32] Apelin injection increases water intake[6] and apelin decreases the hypothalamic secretion of the antidiuretic hormone vasopressin.[33] This diuretic effect of apelin in association with its hypotensive effect participates in the homeostatic regulation of body fluid.  Apelin is also detected in brain areas which control appetite, but its effects on food intake are very contradictory.[34][35][36]Adipose tissue[edit]Apelin is expressed and secreted by adipocytes, and its production is increased during adipocyte differentiation and is stimulated by insulin.[37] Most obese people have elevated levels of insulin, which may therefore be the reason why obese people have been reported to also have elevated levels of apelin.[37]Digestive[edit]Apelin receptor is expressed in several cell types of the gastro-intestinal tract\u00a0: stomach enterochromaffine-like cells;[38][39] unknown cells of endocrine pancreas,[40]colon epithelial cells.[41]In stomach, activation of receptors on enterochromaffine-like cells by apelin secreted by parietal cells can inhibit histamine release by enterochromaffine-like cells, which in turn decreases acid secretion by parietal cells.[39] In pancreas, apelin inhibits  the insulin secretion induced by glucose.[42] This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production.[37] Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels glycemia.[43]Bone[edit]Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.[44]Muscle aging[edit]Muscle apelin expression decreases with age in rodents and humans.[45] By supplementing aged mice with exogenous apelin, Cedric Dray, Philippe Valet, and their colleagues demonstrated that the peptide was able to promote muscle hypertrophy and consequently induced a gain in strength.[45] This study also demonstrated that apelin targets muscle cells during aging by different and complementary pathways: it acts on muscle metabolism by activating an AMPK-dependent mitochondria biogenesis, it promotes autophagy and decreases inflammation in aged mice.[45] Moreover, apelin receptor is also present on muscle stem cells and promotes in vitro and in vivo cellular proliferation and differentiation of these cells into mature muscle cells that participate in muscle regeneration. Finally, muscle apelin could be used a biomarker of physical exercise success in aged individual since its production is correlated to the benefit of a chronic physical exercise in aged individuals.[45]In late 2022, the longevity therapeutics company BioAge announced that its licensed, orally-available apelin receptor agonist BGE-105 had greatly decreased muscle loss and sustained muscle quality and muscle protein synthesis during 10 days of bed rest  in healthy volunteers aged 65 or older participating in a double-blind, placebo-controlled Phase 1b trial.[46] They plan to proceed to a Phase 2 trial in older patients who are on ventilators in the intensive care unit (ICU). Such patients suffer both diaphragm atrophy (the weakening of the muscles that allow one to inhale and exhale, which atrophy dangerously due to disuse during time on a ventilator[47][48][49]) and critical illness myopathy (the broad weakening of the muscles during extended bed rest]]. Each of these conditions are associated with poor functional recovery and substantially increased risk of death after illness.[46]References[edit]^ a b c GRCh38: Ensembl release 89: ENSG00000171388 – Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037010 – Ensembl, May 2017^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ a b c Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M (1998). “Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor”. Biochem. Biophys. Res. Commun. 251 (2): 471\u20136. doi:10.1006\/bbrc.1998.9489. PMID\u00a09792798.^ a b c d Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, Osmond DH, George SR, O’Dowd BF (2000). “Characterization of apelin, the ligand for the APJ receptor”. J. Neurochem. 74 (1): 34\u201341. doi:10.1046\/j.1471-4159.2000.0740034.x. PMID\u00a010617103. S2CID\u00a06548112.^ a b Szokodi I, Tavi P, F\u00f6ldes G, Voutilainen-Myllyl\u00e4 S, Ilves M, Tokola H, Pikkarainen S, Piuhola J, Rys\u00e4 J, T\u00f3th M, Ruskoaho H (2002). “Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility”. Circ. Res. 91 (5): 434\u201340. doi:10.1161\/01.RES.0000033522.37861.69. PMID\u00a012215493.^ Kleinz MJ, Davenport AP (2005). “Emerging roles of apelin in biology and medicine”. Pharmacol. Ther. 107 (2): 198\u2013211. doi:10.1016\/j.pharmthera.2005.04.001. 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PMID\u00a017336906.^ Zeng XX, Wilm TP, Sepich DS, Solnica-Krezel L (March 2007). “Apelin and its receptor control heart field formation during zebrafish gastrulation”. Dev. Cell. 12 (3): 391\u2013402. doi:10.1016\/j.devcel.2007.01.011. PMID\u00a017336905.^ Berry MF, Pirolli TJ, Jayasankar V, Burdick J, Morine KJ, Gardner TJ, Woo YJ (September 2004). “Apelin has in vivo inotropic effects on normal and failing hearts”. Circulation. 110 (11 Suppl 1): II187\u201393. doi:10.1161\/01.CIR.0000138382.57325.5c. PMID\u00a015364861.^ Ashley EA, Powers J, Chen M, Kundu R, Finsterbach T, Caffarelli A, Deng A, Eichhorn J, Mahajan R, Agrawal R, Greve J, Robbins R, Patterson AJ, Bernstein D, Quertermous T (January 2005). “The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo”. Cardiovasc. Res. 65 (1): 73\u201382. doi:10.1016\/j.cardiores.2004.08.018. PMC\u00a02517138. PMID\u00a015621035.^ Kuba K, Zhang L, Imai Y, Arab S, Chen M, Maekawa Y, Leschnik M, Leibbrandt A, Markovic M, Makovic M, Schwaighofer J, Beetz N, Musialek R, Neely GG, Komnenovic V, Kolm U, Metzler B, Ricci R, Hara H, Meixner A, Nghiem M, Chen X, Dawood F, Wong KM, Sarao R, Cukerman E, Kimura A, Hein L, Thalhammer J, Liu PP, Penninger JM (August 2007). “Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload”. Circ. Res. 101 (4): e32\u201342. doi:10.1161\/CIRCRESAHA.107.158659. PMID\u00a017673668.^ Principe A, Melgar-Lesmes P, Fern\u00e1ndez-Varo G, Del Arbol LR, Ros J, Morales-Ruiz M, Bernardi M, Arroyo V, Jim\u00e9nez W (2008). “The hepatic apelin system: A new therapeutic target for liver disease”. Hepatology. 48 (4): 1193\u20131201. doi:10.1002\/hep.22467. PMID\u00a018816630.^ Kechyn S, Barnes G, Howard L (2015). “Assessing dynamic changes in plasma apelin concentration in response to maximal exercise in man”. European Respiratory Journal. 46: PA2316. doi:10.1183\/13993003.congress-2015.PA2316.^ Kechyn, Svyatoslav; Barnes, Gareth; Thongmee, Akaphot; Howard, Luke (September 2015). “Effect of apelin on cardiopulmonary performance during endurance exercise”. European Respiratory Journal (46 suppl 59): 2241. doi:10.1183\/13993003.congress-2015.PA2241.^ O’Carroll AM, Selby TL, Palkovits M, Lolait SJ (June 2000). “Distribution of mRNA encoding B78\/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues”. Biochim. Biophys. Acta. 1492 (1): 72\u201380. doi:10.1016\/S0167-4781(00)00072-5. PMID\u00a011004481.^ De Mota et al., 2000^ De Mota N, Lenkei Z, Llorens-Cort\u00e8s C (December 2000). “Cloning, pharmacological characterization and brain distribution of the rat apelin receptor”. Neuroendocrinology. 72 (6): 400\u20137. doi:10.1159\/000054609. PMID\u00a011146423. S2CID\u00a039313631.^ Taheri S, Murphy K, Cohen M, Sujkovic E, Kennedy A, Dhillo W, Dakin C, Sajedi A, Ghatei M, Bloom S (March 2002). “The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats”. Biochem. Biophys. Res. Commun. 291 (5): 1208\u201312. doi:10.1006\/bbrc.2002.6575. PMID\u00a011883945.^ Sunter D, Hewson AK, Dickson SL (December 2003). “Intracerebroventricular injection of apelin-13 reduces food intake in the rat”. Neurosci. Lett. 353 (1): 1\u20134. doi:10.1016\/S0304-3940(03)00351-3. PMID\u00a014642423. S2CID\u00a043645121.^ O’Shea M, Hansen MJ, Tatemoto K, Morris MJ (June 2003). “Inhibitory effect of apelin-12 on nocturnal food intake in the rat”. Nutr Neurosci. 6 (3): 163\u20137. doi:10.1080\/1028415031000111273. PMID\u00a012793520. S2CID\u00a037941683.^ a b c Boucher J, Masri B, Daviaud D, Gesta S, Guign\u00e9 C, Mazzucotelli A, Castan-Laurell I, Tack I, Knibiehler B, Carp\u00e9n\u00e9 C, Audigier Y, Saulnier-Blache JS, Valet P (April 2005). “Apelin, a newly identified adipokine up-regulated by insulin and obesity”. Endocrinology. 146 (4): 1764\u201371. doi:10.1210\/en.2004-1427. PMID\u00a015677759.^ Wang G, Anini Y, Wei W, Qi X, OCarroll AM, Mochizuki T, Wang HQ, Hellmich MR, Englander EW, Greeley GH (March 2004). “Apelin, a new enteric peptide: localization in the gastrointestinal tract, ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin secretion”. Endocrinology. 145 (3): 1342\u20138. doi:10.1210\/en.2003-1116. PMID\u00a014670994.^ a b Lambrecht NW, Yakubov I, Zer C, Sachs G (March 2006). “Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion”. Physiol. Genomics. 25 (1): 153\u201365. doi:10.1152\/physiolgenomics.00271.2005. PMID\u00a016403840.^ Sorhede Winzell et al., 2005^ Wang G, Kundu R, Han S, Qi X, Englander EW, Quertermous T, Greeley GH (August 2009). “Ontogeny of apelin and its receptor in the rodent gastrointestinal tract”. Regul. Pept. 158 (1\u20133): 32\u20139. doi:10.1016\/j.regpep.2009.07.016. PMC\u00a02761510. PMID\u00a019660504.^ S\u00f6rhede Winzell M, Magnusson C, Ahr\u00e9n B (November 2005). “The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice”. Regul. Pept. 131 (1\u20133): 12\u20137. doi:10.1016\/j.regpep.2005.05.004. PMID\u00a015970338. S2CID\u00a018224695.^ Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Bul\u00e9on M, Cani PD, Attan\u00e9 C, Guign\u00e9 C, Carp\u00e9n\u00e9 C, Burcelin R, Castan-Laurell I, Valet P (November 2008). “Apelin stimulates glucose utilization in normal and obese insulin-resistant mice”. Cell Metab. 8 (5): 437\u201345. doi:10.1016\/j.cmet.2008.10.003. PMID\u00a019046574.^ Xie H, Tang SY, Cui RR, Huang J, Ren XH, Yuan LQ, Lu Y, Yang M, Zhou HD, Wu XP, Luo XH, Liao EY (May 2006). “Apelin and its receptor are expressed in human osteoblasts”. Regul. Pept. 134 (2\u20133): 118\u201325. doi:10.1016\/j.regpep.2006.02.004. PMID\u00a016563531. S2CID\u00a020819559.^ a b c d Vinel, Claire; Lukjanenko, Laura; Batut, Aurelie; Deleruyelle, Simon; Prad\u00e8re, Jean-Philippe; Le Gonidec, Sophie; Dortignac, Alliz\u00e9e; Geoffre, Nancy; Pereira, Oph\u00e9lie; Karaz, Sonia; Lee, Umi; Camus, Myl\u00e8ne; Chaoui, Karima; Mouisel, Etienne; Bigot, Anne; Mouly, Vincent; Vigneau, Mathieu; Pagano, Allan; Chopard, Ang\u00e8le; Pillard, Fabien; Guyonnet, Sophie; Cesari, Matteo; Burlet, Odile; Pahor, Marco; Feige, Jerome; Vellas, Bruno; Valet, Philippe; Dray, Cedric (30 July 2018). “The exerkine apelin reverses age-associated sarcopenia”. Nature Medicine. 24 (9): 1360\u20131371. doi:10.1038\/s41591-018-0131-6. PMID\u00a030061698. S2CID\u00a051876150.^ a b “BioAge Announces Positive Topline Results for BGE-105 in Phase 1b Clinical Trial Evaluating Muscle Atrophy in Older Volunteers at Bed Rest”. BusinessWire. 5 December 2022. Retrieved 14 January 2023.^ Jaber S, Petrof BJ, Jung B, Chanques G, Berthet JP, Rabuel C,  et\u00a0al. (February 2011). “Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans”. American Journal of Respiratory and Critical Care Medicine. 183 (3): 364\u2013371. doi:10.1164\/rccm.201004-0670OC. PMID\u00a020813887.^ Goligher EC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS,  et\u00a0al. (January 2018). “Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes”. American Journal of Respiratory and Critical Care Medicine. 197 (2): 204\u2013213. doi:10.1164\/rccm.201703-0536OC. PMID\u00a028930478. S2CID\u00a03716085.^ Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P,  et\u00a0al. (March 2008). “Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans”. The New England Journal of Medicine. 358 (13): 1327\u20131335. doi:10.1056\/NEJMoa070447. PMID\u00a018367735.Further reading[edit]Lee DK, George SR, O’Dowd BF (2006). “Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity”. Trends Pharmacol. Sci. 27 (4): 190\u20134. doi:10.1016\/j.tips.2006.02.006. PMID\u00a016530855.Lee DK, Saldivia VR, Nguyen T, Cheng R, George SR, O’Dowd BF (2005). “Modification of the terminal residue of apelin-13 antagonizes its hypotensive action”. Endocrinology. 146 (1): 231\u20136. doi:10.1210\/en.2004-0359. PMID\u00a015486224.Lee DK, Lan\u00e7a AJ, Cheng R, Nguyen T, Ji XD, Gobeil F, Chemtob S, George SR, O’Dowd BF (2004). “Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors”. J. Biol. Chem. 279 (9): 7901\u20138. doi:10.1074\/jbc.M306377200. PMID\u00a014645236.O’Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T (1993). “A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11”. Gene. 136 (1\u20132): 355\u201360. doi:10.1016\/0378-1119(93)90495-O. PMID\u00a08294032.Chun HJ, Ali ZA, Kojima Y, Kundu RK, Sheikh AY, Agrawal R, Zheng L, Leeper NJ, Pearl NE, Patterson AJ, Anderson JP, Tsao PS, Lenardo MJ, Ashley EA, Quertermous T (October 2008). “Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis”. The Journal of Clinical Investigation. 118 (10): 3343\u201354. doi:10.1172\/JCI34871. PMC\u00a02525695. PMID\u00a018769630.Barnes G, Japp AG, Newby DE (July 2010). “Translational promise of the apelin–APJ system”. Heart. 96 (13): 1011\u20136. doi:10.1136\/hrt.2009.191122. PMID\u00a020584856. S2CID\u00a021522978.External links[edit]     (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4"},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/apelin-wikipedia\/#breadcrumbitem","name":"Apelin – Wikipedia"}}]}]