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User:Kf7tgy22/Hepcidin/Bibliography

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This image depicts the structure of Ferroportin with Hepcidin bound. The original image was modified to exclude the Fragment Antigen used to image the protein.
Ferroportin, Hepcidin, Iron Transporter

Regulation

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Hepcidin synthesis and secretion by the liver is controlled by iron stores, inflammation (hepcidin is an acute phase reactant), hypoxia, and erythropoiesis.[1] In response to large iron stores, production of Bone Morphogenic Protein (BMP) is induced, which binds to receptors on hepatocytes and induces hepcidin expression via the SMAD pathway.[2] Inflammation causes an increase in hepcidin production by releasing the signaling molecule interleukin-6 (IL-6), which binds to a receptor and upregulates the HAMP gene via the JAK/STAT pathway[2]. Hypoxia negatively regulates hepcidin production via production the transcription factor hypoxia-inducible factor (HIF), which under normal conditions is degraded by von Hippel-Lindau (VHL) and prolyl dehydrogenase (PHD). When hypoxia is induced, however, PHD is inactivated, thus allowing HIF to down-regulate hepcidin production. Erythropoiesis decreases hepcidin production via production of erythropoietin (EPO), which has been shown to down-regulate hepcidin production.[2]

Severe anemia is associated with low hepcidin levels, even in the presence of inflammation.[3] Erythroferrone, produced in erythroblasts, has been identified as inhibiting hepcidin and so providing more iron for hemoglobin synthesis in situations such as stress erythropoiesis.[4][5]

Vitamin D has been shown to decrease hepcidin, in cell models looking at transcription and when given in large doses to human volunteers. Optimal function of hepcidin may be predicated upon the adequate presence of vitamin D in the blood.[6]



Function

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Hepcidin is a regulator of iron metabolism. It inhibits iron transport by binding to the iron export channel ferroportin which is located in the basolateral plasma membrane of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages), ultimately resulting in ferroportin breakdown in lysosomes.[7][8] It has been shown that Hepcidin is able to bind to the central cavity of Ferroportin, thus occluding iron export from the cell. This suggests that Hepcidin is able to regulate iron export independently of Ferroportin endocytosis and ubiquitination, and is thus quickly inducible and reversible.[9][10] In enterocytes, this prevents iron transmission into the hepatic portal system, thereby reducing dietary iron absorption. In macrophages, ferroportin inhibition causes iron sequestration within the cell. Increased hepcidin activity is partially responsible for reduced iron availability seen in anemia of chronic inflammation, such as kidney failure and that may explain why patient with end stage renal failure may not respond to oral Iron replacement .[11]

Any one of several mutations in hepcidin result in juvenile hemochromatosis. The majority of juvenile hemochromatosis cases are due to mutations in hemojuvelin.[12] Mutations in TMPRSS6 can cause anemia through dysregulation of Hepcidin.[13]

Hepcidin has strong antimicrobial activity against Escherichia coli strain ML35P and Neisseria cinerea and weaker antimicrobial activity against Staphylococcus epidermidis, Staphylococcus aureus and Streptococcus agalactiae. It is also active against the fungus Candida albicans, but has no activity against Pseudomonas aeruginosa.[14]


Bibliography

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This is where you will compile the bibliography for your Wikipedia assignment. Add the name and/or notes about what each source covers, then use the "Cite" button to generate the citation for that source

  • Sharraya Aschemeyer, Bo Qiao, Deborah Stefanova, Erika V. Valore, Albert C. Sek, T. Alex Ruwe, Kyle R. Vieth, Grace Jung, Carla Casu, Stefano Rivella, Mika Jormakka, Bryan Mackenzie, Tomas Ganz, Elizabeta Nemeth (2018). "Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin". Blood 131 (8): 899–910.[9]
    • This is a paper that determines the inhibition site of Hepcidin on Ferroportin. It's from a peer reviewed journal, so it should be pretty trustworthy.
  • Nemeth, E.; Ganz, T. Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis. Int. J. Mol. Sci. 2021, 22, 6493. https://doi.org/10.3390/ijms22126493[10]
    • This is a recent review paper that characterizes hepcidin-ferroportin interactions in iron regulation.
  • Gautam Rishi, Daniel F. Wallace, V. Nathan Subramaniam (2015-06-01). "Hepcidin: regulation of the master iron regulator". Biosci Rep 35 (3): e00192.[2]
    • This is a review article consolidating the recent work on how Hepcidin regulates Iron

References

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  1. ^ Zhao, Ningning; Zhang, An-Sheng; Enns, Caroline A. (2013-06-03). "Iron regulation by hepcidin". Journal of Clinical Investigation. 123 (6): 2337–2343. doi:10.1172/JCI67225. ISSN 0021-9738. PMC 3668831. PMID 23722909.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ a b c d Rishi, Gautam; Wallace, Daniel F.; Subramaniam, V. Nathan (2015-05-19). "Hepcidin: regulation of the master iron regulator". Bioscience Reports. 35 (3). doi:10.1042/bsr20150014. ISSN 0144-8463. PMC 4438303. PMID 26182354.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ Abuga, Kelvin M.; Muriuki, John Muthii; Uyoga, Sophie M.; Mwai, Kennedy; Makale, Johnstone; Mogire, Reagan M.; Macharia, Alex W.; Mohammed, Shebe; Muthumbi, Esther; Mwarumba, Salim; Mturi, Neema; Bejon, Philip; Scott, J. Anthony G.; Nairz, Manfred; Williams, Thomas N. (2021-09-09). "Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia". Haematologica. 107 (7): 1589–1598. doi:10.3324/haematol.2021.279316. ISSN 1592-8721. PMC 9244826. PMID 34498446.{{cite journal}}: CS1 maint: PMC format (link)
  4. ^ "Erythroferrone: A Missing Link in Iron Regulation". web.archive.org. 2019-01-28. Retrieved 2022-11-04.
  5. ^ Kautz, Léon; Jung, Grace; Valore, Erika V.; Rivella, Stefano; Nemeth, Elizabeta; Ganz, Tomas (2014-06-01). "Identification of erythroferrone as an erythroid regulator of iron metabolism". Nature Genetics. 46 (7): 678–684. doi:10.1038/ng.2996. ISSN 1546-1718. PMC 4104984. PMID 24880340.{{cite journal}}: CS1 maint: PMC format (link)
  6. ^ Bacchetta, Justine; Zaritsky, Joshua J.; Sea, Jessica L.; Chun, Rene F.; Lisse, Thomas S.; Zavala, Kathryn; Nayak, Anjali; Wesseling-Perry, Katherine; Westerman, Mark; Hollis, Bruce W.; Salusky, Isidro B.; Hewison, Martin (2014-02-28). "Suppression of Iron-Regulatory Hepcidin by Vitamin D". Journal of the American Society of Nephrology. 25 (3): 564–572. doi:10.1681/ASN.2013040355. ISSN 1046-6673. PMC 3935584. PMID 24204002.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ Rossi, Enrico (2005-08). "Hepcidin - the Iron Regulatory Hormone". Clinical Biochemist Reviews. 26 (3): 47–49. ISSN 0159-8090. PMC 1240030. PMID 16450011. {{cite journal}}: Check date values in: |date= (help)
  8. ^ Gulec, Sukru; Anderson, Gregory J.; Collins, James F. (2014-08-15). "Mechanistic and regulatory aspects of intestinal iron absorption". American Journal of Physiology-Gastrointestinal and Liver Physiology. 307 (4): G397–G409. doi:10.1152/ajpgi.00348.2013. ISSN 0193-1857. PMC 4137115. PMID 24994858.{{cite journal}}: CS1 maint: PMC format (link)
  9. ^ a b Aschemeyer, Sharraya; Qiao, Bo; Stefanova, Deborah; Valore, Erika V.; Sek, Albert C.; Ruwe, T. Alex; Vieth, Kyle R.; Jung, Grace; Casu, Carla; Rivella, Stefano; Jormakka, Mika; Mackenzie, Bryan; Ganz, Tomas; Nemeth, Elizabeta (2018-02-22). "Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin". Blood. 131 (8): 899–910. doi:10.1182/blood-2017-05-786590. ISSN 0006-4971. PMC 5824336. PMID 29237594.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ a b Nemeth, Elizabeta; Ganz, Tomas (2021-06-17). "Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis". International Journal of Molecular Sciences. 22 (12): 6493. doi:10.3390/ijms22126493. ISSN 1422-0067. PMC 8235187. PMID 34204327.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  11. ^ Gulec, Sukru; Anderson, Gregory J.; Collins, James F. (2014-08-15). "Mechanistic and regulatory aspects of intestinal iron absorption". American Journal of Physiology-Gastrointestinal and Liver Physiology. 307 (4): G397–G409. doi:10.1152/ajpgi.00348.2013. ISSN 0193-1857. PMC 4137115. PMID 24994858.{{cite journal}}: CS1 maint: PMC format (link)
  12. ^ Gulec, Sukru; Anderson, Gregory J.; Collins, James F. (2014-08-15). "Mechanistic and regulatory aspects of intestinal iron absorption". American Journal of Physiology-Gastrointestinal and Liver Physiology. 307 (4): G397–G409. doi:10.1152/ajpgi.00348.2013. ISSN 0193-1857. PMC 4137115. PMID 24994858.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ Acton, Q. Ashton (2012). Iron-Deficiency Anemia ScholarlyPaper. Atlanta, GA: Scholarly Media LLC. ISBN 978-1-4649-8960-5. OCLC 1247675624.
  14. ^ "UniProt". www.uniprot.org. Retrieved 2022-11-04.
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