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Simulated microgravity decreases circulating iron in rats: role of inflammation-induced hepcidin upregulation.

التفاصيل البيبلوغرافية
العنوان: Simulated microgravity decreases circulating iron in rats: role of inflammation-induced hepcidin upregulation.
المؤلفون: Cavey, Thibault, Pierre, Nicolas, Nay, Kevin, Allain, Coralie, Ropert, Martine, Loreal, Olivier, Derbre, Frederic
المصدر: Experimental Physiology, 102 (3), 291-298 (2017)
بيانات النشر: Blackwell
سنة النشر: 2017
المجموعة: University of Liège: ORBi (Open Repository and Bibliography)
مصطلحات موضوعية: Animals, Hepcidins/metabolism, Hindlimb Suspension/physiology, Inflammation/blood/metabolism/physiopathology, Interleukin-6/metabolism, Iron/blood, Liver/metabolism/physiopathology, Male, RNA, Messenger/metabolism, Rats, Wistar, STAT3 Transcription Factor/metabolism, Signal Transduction/physiology, Space Flight/methods, Transcriptional Activation/physiology, Up-Regulation/physiology, Weightlessness, Life sciences, Biochemistry, biophysics & molecular biology, Sciences du vivant, Biochimie, biophysique & biologie moléculaire
الوصف: peer reviewed ; NEW FINDINGS: What is the central question of this study? Although microgravity is well known to reduce circulating iron in astronauts, the underlying mechanism is still unknown. We investigated whether hepcidin, a key hormone regulating iron metabolism, could be involved in this deleterious effect. What is the main finding and its importance? We show that hindlimb suspension, a model of microgravity, stimulates the production of hepcidin in liver of rats. In agreement with the biological role of hepcidin, we found a decrease of circulating iron and an increase of spleen iron content in hindlimb-unloaded rats. Consequently, our study supports the idea that hepcidin could play a role in the alteration of iron metabolism parameters observed during spaceflight. During spaceflight, humans exposed to microgravity exhibit an increase of iron storage and a reduction of circulating iron. Such perturbations could promote oxidative stress and anaemia in astronauts. The mechanism by which microgravity modulates iron metabolism is still unknown. Herein, we hypothesized that microgravity upregulates hepcidin, a hormone produced by the liver that is the main controller of iron homeostasis. To test this hypothesis, rats were submitted to hindlimb unloading (HU), the reference model to mimic the effects of microgravity in rodents. After 7 days, the mRNA level of hepcidin was increased in the liver of HU rats (+74%, P = 0.001). In agreement with the biological role of hepcidin, we found an increase of spleen iron content (+78%, P = 0.030) and a decrease of serum iron concentration (-35%, P = 0.002) and transferrin saturation (-25%, P = 0.011) in HU rats. These findings support a role of hepcidin in microgravity-induced iron metabolism alteration. Furthermore, among the signalling pathways inducing hepcidin mRNA expression, we found that only the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) axis was activated by HU, as shown by the increase of phospho-STAT3 (+193%, P < 0.001) ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 0958-0670
1469-445X
العلاقة: urn:issn:0958-0670; urn:issn:1469-445X; https://orbi.uliege.be/handle/2268/237021Test; info:hdl:2268/237021; https://orbi.uliege.be/bitstream/2268/237021/1/Cavey%20et%20al.%20-%20Microgravity%20hepcidin%20-%20Revised%20final%20version.pdfTest; scopus-id:2-s2.0-85014080960; info:pmid:28087888
DOI: 10.1113/EP086188
الإتاحة: https://doi.org/10.1113/EP086188Test
https://orbi.uliege.be/handle/2268/237021Test
https://orbi.uliege.be/bitstream/2268/237021/1/Cavey%20et%20al.%20-%20Microgravity%20hepcidin%20-%20Revised%20final%20version.pdfTest
حقوق: open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.720367F1
قاعدة البيانات: BASE
الوصف
تدمد:09580670
1469445X
DOI:10.1113/EP086188