Apelin
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Location (UCSC) | Chr X: 129.65 – 129.65 Mb | Chr X: 47.11 – 47.12 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene.
Discovery
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
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
The sites of receptor expression are linked to the different functions played by apelin in the organism.
Vascular
Vascular expression of the
Cardiac
The apelin receptor is expressed early during the
Exercise
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
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
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
Apelin receptor is expressed in several cell types of the
Bone
Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.[44]
Muscle aging
Muscle apelin expression decreases with age in rodents and humans.
In late 2022, the
References
- ^ 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.
- ^ PMID 9792798.
- ^ S2CID 6548112.
- ^ PMID 12215493.
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- ^ De Mota et al., 2000
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- ^ PMID 15677759.
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- ^ Sorhede Winzell et al., 2005
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- ^ BusinessWire. 5 December 2022. Retrieved 14 January 2023.
- PMID 20813887.
- S2CID 3716085.
- PMID 18367735.
Further reading
- 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): 190–4. PMID 16530855.
- 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): 231–6. PMID 15486224.
- Lee DK, Lança 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): 7901–8. PMID 14645236.
- 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 (1–2): 355–60. PMID 8294032.
- 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): 3343–54. PMID 18769630.
- Barnes G, Japp AG, Newby DE (July 2010). "Translational promise of the apelin--APJ system". Heart. 96 (13): 1011–6. S2CID 21522978.
External links
- Apelin+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "Apelin". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2021-08-16. Retrieved 2007-10-25.
- Human APLN genome location and APLN gene details page in the UCSC Genome Browser.