ABSTRACT
BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.
Subject(s)
Humans , Gene Expression Regulation, Neoplastic/genetics , Hepatocytes/metabolism , SOXB1 Transcription Factors/genetics , Hepcidins/genetics , Plasmids/genetics , Binding Sites , Interleukin-6/metabolism , Promoter Regions, Genetic/genetics , Bone Morphogenetic Protein 2/metabolism , SOXB1 Transcription Factors/metabolism , Gene Knockdown Techniques , Hep G2 Cells , Hepcidins/metabolism , Genetic Vectors , Anemia/genetics , Anemia/metabolism , Iron/metabolism , LuciferasesABSTRACT
Age and growth parameters were estimated for bigeye tuna Thunnus obesus Lowe, 1839 sampled from China longline fisheries in the central Atlantic Ocean from October 2002 to July 2003 and from August 2004 to March 2005. The von Bertalanffy growth parameters were estimated at L8=217.9 cm fork length, k=0.23 year-1, and t0=-0.44 year. The total mortality rate (Z) was estimated to be from 0.82 to 1.02, the fishing mortality (F) and the natural mortality were 0.54 year-1 and 0.39 year-1, respectively. The exploitation ratio (E) was 0.35. This study provides the detailed estimates of growth and mortality rate for bigeye tuna in the central Atlantic Ocean, which can be used as biological input parameters in further stock evaluations in this region. However, age analysis, additional validation of the size composition and stock structure are needed for future studies. Rev. Biol. Trop. 57 (1-2): 79-88. Epub 2009 June 30.