tailieunhanh - Báo cáo khoa học: a-1 Antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum

Recent discoveries have indicated that the hormone hepcidin plays a major role in the control of iron homeostasis. Hepcidin regulates the iron level in the blood through the interaction with ferroportin, an iron exporter molecule, causing its internalization and degradation. | ễFEBS Journal a-1 Antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum 1 I I-V I 1 I I K I 1_2ifi. Al -2 1 II 1 A. . I AH .2 I Edina Pandur Judit Nagy Viktor S. Poor Akos Sarnyai Andras Huszar Attila Miseta and Katalin Sipos1 1 Department of Forensic Medicine University of Pecs Hungary 2 Institute of Laboratory Medicine University of Pecs Hungary Keywords blood serum cellular transport hepcidin iron transport a-1 antitrypsin Correspondence K. Sipos Department of Forensic Medicine University of Pecs 12 Szigeti ut Pecs H-7624 Hungary Fax 36 72 536 242 Tel 36 72 536 230 E-mail Received 13 November 2008 revised 22 January 2009 accepted 26 January 2009 doi Recent discoveries have indicated that the hormone hepcidin plays a major role in the control of iron homeostasis. Hepcidin regulates the iron level in the blood through the interaction with ferroportin an iron exporter molecule causing its internalization and degradation. As a result hepcidin increases cellular iron sequestration and decreases the iron concentration in the plasma. Only mature hepcidin result of the cleavage of prohepcidin by furin proteases has biological activity however prohepcidin the prohormone form is also present in the plasma. In this study we aimed to identify new protein-protein interactions of preprohepcidin prohepcidin and hepcidin using the BacterioMatch two-hybrid system. Screening assays were carried out on a human liver cDNA library. Preprohepcidin screening gave the following results a-1 antitrypsin transthyretin and a-1-acid glycoprotein showed strong interactions with preprohepcidin. We further confirmed and examined the a-1 antitrypsin binding in vitro glutathione S-transferase pull down coimmunoprecipitation MALDI-TOF and in vivo ELISA cross-linking assay . Our results demonstrated that the serine protease inhibitor a-1 antitrypsin binds preprohepcidin within the cell during maturation. .