Cystathionine beta-synthase is required for body iron homeostasis
Publication in refereed journal

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摘要Cystathionine β‐synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin‐6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS−/−) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis‐like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin‐6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2–related factor‐2 and an up‐regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS‐overexpressing adenovirus into CBS mutant mice could partially reverse the iron‐related phenotype. Conclusion: Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis‐like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS.
著者Yu-Fu ZHOU, Xiao-Mei WU, Gan ZHOU, Ming-dao MU, Fa-Li ZHANG, Fe-Mi LI, Christopher QIAN, Fang DU, Wing-Ho YUNG, Zhong-Ming QIAN, Ya KE
期刊名稱Hepatology
出版年份2018
月份1
卷號67
期次1
出版社WILEY
頁次21 - 35
國際標準期刊號0270-9139
電子國際標準期刊號1527-3350
語言英式英語
Web of Science 學科類別Gastroenterology & Hepatology;Gastroenterology & Hepatology

上次更新時間 2020-31-10 於 01:19