2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Duan, XL

Fu, LJ

Qian, ZM

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishedVoR allowe

PolyU Institutional Repository

??????? hepcid in*付丽娟 1　段相林 1　钱忠明 1, 2　常彦忠 1, △(1?????????????????????? , ??? 050016;2?????????????????)??　铁是机体必需的营养元素 。然而 ,铁过载则导致细胞的损伤 。由于生物体缺少排泄铁的机制 ,因而 ,肠铁吸收的调控便成为维持机体铁稳态的关键 。新近研究发现 hepcidin对机体铁稳态的调节起着至关重要的作用 ,被人们称为铁调节激素。 Hepcidin主要在肝细胞中合成 ,之后分泌至血液将体内铁需要的信号传至小肠 ,调控肠铁的吸收 。这一过程主要通过调节小肠铁转运相关蛋白的表达而实现。任何影响 hepcidin表达的因素都可能破坏体内的铁平衡 ,造成铁代谢相关疾病 。???　铁代谢;铁调素;遗传性血色素病;贫血?????　Q493　　???????????? ,?????????????? (Fe3+)???? 。?????????? ,????????????? ,????????????? ,??? 、????? 。??????????????????????? ,????????????????????。???????????? 、????? 、DNA?????????? 。?? ,?????????????:????????? ,????????? ,??????????????????? ,????????????。??????????????????????????? 。?? ,????????????????????。??? ,??????????:?????????(d iva lent-me tal transporter 1, DMT1) (Gunsh in.1997)、??????( ferroportin 1 , FP1)(Donovan.2000)、?????????? (hephaestin, HP)(V ulpe. 1999)、????? b(duodenal cy tochromeb, Dcy tb)(M cK ie. 2001)、?????? 2 ( transfe r-rin receptor 2, TfR2)(???. 2003)? HFE?????????(Roy. 2004),?????????????????? ,?????? (hepc id in)[ 1, 2]??? ,??????????????????。? 、?????????????????????? 。??????????????????:?????????????????? ,?????????????? 。 Fe3+??????????? ,????????? Dcy tb? Fe3+?????? Fe2+ ,???????????? DMT1???? 。?????????????:(1)???? ( ferritin)??????? ,?????;(2)???????????????;(3)?? FP1? HP???????????? ,????????? 。?? ,????? DMT1????? FP1? HP?????????????? 。? 、?????? 、?? 、?????????????????????????( transferrin, Tf)。? Tf???? Fe3+,??????????? Fe2+????? , HP?????(Cerulop lasm in, CP)(???. 2002)??????? Fe3+,????? Tf??。?? T f????????? Fe3+。?? ,???????????Tf:?????? (Fe2-T f)、??????(Fe-Tf)??????? (Apo-Tf)。?????????????? Fe-Tf,????????? Fe2-Tf????。?? Tf??????????????(TfRs)?? ,? Fe2-Tf? TfRs????? Fe-Tf?4? ,? A po-T f? 24?。?? Fe2-Tf?????????? Fe-Tf。????? ,???????????????????? TfR?????????。????????????? 3000 ～ 4000mg,?? 2 /3??????????? 。????????? TfRs????????????? ,???*????????????????????????△???? 233 ?????? 2005?? 36?? 3?????????:(1)??;(2)??;(3)??;(4)?????;(5)??;(6)??????;(7)Apo-T f?????。?? , Fe2-Tf???????? TfRs? ,?? Fe2-Tf-TfR??????????????????????????;???????? ,?????? pH???? 5 ～ 6,??? Tf?????????? ,???? DMT1???????;?? , Apo-Tf-T fR?????????????? , Tf???????????。?????????????????????????????????? [ 3] 。??????????? 12. 5% ～ 25%???????? ,???????????? 。??????? ,???????? TfR1?? Fe2-Tf,????????????????? TfR2?? 。?? ,???????????????? Fe2-Tf。?? ,?????????????? ,?????? FP1???。?? ,????? 1 ～ 2mg? ,????????????? 20mg。???????? ,??????????????????? ,??????????[ 4] 。?????????????(retic-u loendo thelial system , RE)???? 。???????? Hb, Hb???????? (hap tog lobin)???? Hb-??????? ,????????????? CD163????????。?? ,????????????????????? 。???????????????????????????? , ??? FP1???????????? [ 5] 。? 、????????????????????? ,?????????????? 。?? ,??????????????????? 。???????? ,???????;?????????? (Trinder. 2002)。???? ,???????????????????????????????????????????。?????? ,???????????????????????????。??????????????????????????  ?????????????  ??????????????? 。? 、??? hepcid in??????????????????? ,?????????????? [ 1, 2] 。??????? 8????????????????? ,?? 1?? (Hunter. 2002)。???????? ,??USF2、HNF3β、C /EBPβ ? NF-κB ??????(Courselaud. 2002)。???????? 84-aa??? ,????????????????? , 20-aa? 25-aa????????? ,???????????。?????????? 19????? ,?????? 7????? ,?????????????? ,??????????????????? 。?????????? ,?????????? 1???? 2?? ,????? 1????????? (Lou . 2004)。? 1　???????????? ,??????? 、???????????? ,??????? 。?? IL-6????????? mRNA??? (Neme th. 2003)。???????????????? ,????????? ,?????????????。? EPO???? 3??????????????? (N ico las.2002)。???????????? Pigeon? [ 6] ?????。?? N icolas?[ 7]?? USF2??????? ,???????????? ,???????????? , ??????? (he reditary haemo-chroma tosis, HH)、HFE、β2-M ?????? (Flem-ing. 2001, Ahmad. 2002)。??????????? ,???? 、???????? ,??????????????。W einstein???????????????? ,????? Ⅰ??????????????? ,??????????? ,?????????????? ,?????????????? ,??????????????????(Weinste in. 2002)。?????????????? (C70R、G71D),????????????? 234 ?????? 2005?? 36?? 3??? ( juven ile hemochromatosis, JH )(Roe tto. 2004,B iasio tto. 2003)。??????????????????? ,?????? ,???????。?? ,?????????????????????????????? 、?? 、????????????? 。???????? 、?? 、??????? ,????????? ,????????? 。?? ,??? hepcidin??????。????????? ,?????????? ,????Usf2- /-?????????????? ,??????????? ,?? , RE????? ,????? ,?????? 。???????? ,??????? ,?????? ,??????。?? 、?????????????????? ,???????? , RE????? ,????? ,?????。? 、?????????????????????? HFE、 TfR1、TfR2、 FP1、 DMT1 (Zhang. 2004)。 HFE ???MHC1???????? , Fraze r? [ 8]?? HFE???? TfR1???? ,? Tf????????? 。???? Tf?????? HFE????? TfR1??。?? Fe2-Tf?? TfR1???? HFE? ,????? HFE?????? 。????????? ,????????。? HFE? T fR1??? ,????????????。?? ,???????TfR2????????????? 。 Fe2-Tf?TfR2????????? HFE?? ,?????????? 。????????????? ,??? Fe2-Tf? TfR2?? ,?????????。??????? , Fe2-Tf?? ,????? TfR1???? ,????? HFE??? TfR1。?? T fR1?Fe2-Tf????? TfR2? 25? ,??? Fe2-Tf??? , Fe2-Tf? TfR1?????? T fR2,?? TfR2???? Fe2-Tf,??????????? ,??????? ,?????? 。?? , HFE? T fR2??????????????? ,?????? 。?? , HFE、 TfR1? TfR2??? Tf??????????????????????? ,?????? 。??????????????  ?????? ,??????????????????????????????? 。?????????????????? ,???????? ,?????????? 。????????????????(IRPs)???。 DMT1、 ferritin? FP1????IREs、 IRP? IRE??????????????????????????? ,??????? 、????????????? ,??????????????? 。???? ,??????????? HFE???? ,?? β2-???? (β2-M)????? 。?????? HFE??????? ,???????? TfR1???? ,?? TfR1????????????。????????????????? ,????????????????。?????? TfR1 /HFE /β2-M????? 。???????????? ,?? Fe2-Tf? β2-M /HFE /TfR1??????????? , ???????? , IRP?????? ,????????? FP1???? ,??????????? ,???? Tf????? [ 9] 。?? ,??????????????????????????????????????????。 F razer? [ 8]???????? ,???????????????????? ,?? FP1??? ,??????。?? (Frazer. 2003, M illa rd.2004)??? (Yam aj.i 2004)?????????????????????? ,?? DMT1? FP1??? ,??????。?? , Neme th???? Sci-ence???????????????? FP1,?FP1?????????? ,??? FP1?????????? [ 10] 。???? ,?????????????????????。????? ,????? RE??? ,?? Tf???????????????????????? ,??????????。?????????????????????????????????? ,????????????????? ,??????????????。???? , hepcidin???????????????? ,????????????????????? ,?????????????????????? 。?? ,????????????? ,?????????????????? ,?????????????????????????????????? ,????????????。?? ,??????????????? ,????????????? ,?????????????? ,????????????????? 235 ?????? 2005?? 36?? 3????????????????????。? ? ? ?1　Krause A, Ne itz S, M agert H J, e t a.l LEAP-1, a nove lhigh ly disulfide-bonded human peptide, exh ibits antim icro-bial ac tivity. FEBS Le tt, 2000, 480:147 ～ 150.2　Park CH , Va lo re EV, W aringA J, e t a.l H epc id in, a u rina-ry antim icrob ia l pep tide synthesized in the liver. J B io lChem , 2001, 276:7806～ 7810.3　Q ian ZM , L iHY, Sun HZ, e t a .l T arge ted drug delive ry viathe transfe rrin recep to r-m ed ia ted endocy tosis pa thway. Phar-m aco l Rev, 2002, 54:561 ～ 587.4　Ganz T. H epc id in, a key regu la to r o f iron m e tabo lism andmedia to r o f anem ia of inflamm ation. Blood, 2003, 102:783～ 788.5　KnutsonM , W essling-ResnickM. Ironm e tabo lism in the re-ticu loendo thelia l system. Crit Rev BiochemM o l B io l, 2003,38:61 ～ 88.6　P igeon C, Ily in G, Cou rse laud B, e t a.l A new mouse liver-spec ific gene, encoding a pro te in hom ologous to hum an anti-m ic rob ial peptide hepc id in, is overexpre ssed du ring iron o-ve rload. J B iol Chem , 2001, 276:7811 ～ 7819.7　Nico la s G, BennounM , Devaux I, e t a.l Lack o f hepcidingene expression and seve re tissue iron ove rload in upstreamstimu la to ry facto r 2( USF2) knockout m ice. PNAS, 2001,98:8780 ～ 8785.8　F raze rDM , Anderson G J. The o rche stra tion of body iron in-take:how and whe re do entero cy tes rece ive the ir cuesB lood Ce llsM o l D is, 2003, 30:288 ～ 297.9　F lem ing RE, S ly W S. H epc id in:a putative iron-regu la toryhorm one re levant to he redita ry hemochrom atosis and the ane-m ia o f ch ronic d isease. PNAS, 2001, 98:8160 ～ 8162.10　N em eth E, TuttleM S, Pow elson J, e t a.l H epcidin regu-la te s iron e fflux by binding to fe rropo rtin and inducing itsinterna liza tion. Sc ience, 2004, 306:2090 ～ 2093.? ? ? ?????????? ,????????? ,?????????????????????????? 。????? “???? ”。???????? ,?????????????。?? ,?????????????????? (h ttp:/ /www. ns.f gov /sbe /srs /se ind04 /star.t htm ),?????????????? ,???????????????? 。? 2001??????? , 30%?????????????????;?????????? 61%。???????? ,??????????????????。????????????????:?????????????? ,????????????????????????? 。?????????????????? ,?????????? , 42%?????? ,?????????????? 。?????????????????????  ????????? ,???????????????????? ,??????? ,?????????????。???????????? ,??????????????????? ,???????????。????? ,??????????????????????? 。?? ,???????????????????????? 、??? 、?????????????? ,??????????????????????????????。?? ,?????? ,???????。?? ,??????????????? ,???????????? ,????????????????????? ,?? ,?????????????。?? ,?????????????? ,?????????? 。?? ,??????? ,??????????????????? ,????????? ,??????????? ,??????????????? 。????????????? ,????????。??????????? ,?????? 、??????????????? 。(Na tu re Neu rosc ience, 2004, 7:1013)(左艳芳　罗　非) 236 ?????? 2005?? 36?? 3?

铁代谢与铁调素hepcidin

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