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1、综 述I*T:L8?*郭家彬1, 2 铁 璐1 DianaN Krause2 SuePDuckles2 李学军1, v( 1v$D0,100191; 2Fv:snD0)K1 大量研究表明雌激素具有神经保护作用,但其机制尚不清楚b近年来研究提示,雌激素的神经保护作用与线粒体有着密切联系b线粒体是细胞内能量和活性氧自由基(ROS)的主要来源,对细胞内信号转导a细胞存活与死亡调节等具有十分重要的影响b在生理和病理条件下,雌激素可多方面调节线粒体功能,包括影响ATP与 ROS的生成a稳定线粒体膜电位a维护细胞内钙稳态,以及调节线粒体基因和蛋白表达等b本文主要从线粒体角度综述了雌激素神经保护作用及其机制
2、b1oM 雌激素;线粒体;神经保护;活性氧自由基;雌激素受体ms| R972M echanism of E strogen-M ediated N europrotection: R egulation of M itochondrial Function GUOJia-Bin1, 2, TIE Lu1, DianaN Krause2, SueP Duckles2, LIXue-Jun1 (1D epartment of Pharmacology,School of BasicM edical Sciences, Peking University, Beijing100191, China;
3、 2D epartment of Pharmacology,University of California, Irvine, CA 92697, USA)Abstract Numerousstudiesshow theneuroprotectiveeffectsofestrogen, but theunderlyingmechanismstillremainsunclear. Recentstudies indicatethatmitochondriaare critically involved in estrogen-media-ted neuroprotection. Mitochon
4、dria are themain sources of cellular energy and reactive oxygen species(ROS), they play an importantrole in signaling transduction and cellular life-death decisions. Estrogenexertsmultiple effects onmitochondria under physiologicaland/or pathological conditions, these effectsmay includemodulatingATP
5、andROSproduction, preservingmitochondriamembranepotentia,l mainta-iningcalcium homeostasis, and regulatingmitochondrialgeneandprotein expression, etc. In thispaper,wediscussed the neuroprotective effects of estrogen, particularly focused on theunderlyingmechanismsrelated tomitochondria.K ey w ords e
6、strogen; mitochondria; neuroprotection; reactiveoxygen species; estrogen receptorIiI8=B8%?bvV,IA*T,7S1I*TbM?C,I*TL8MbL8bL8VL8n,%Cay0( apoptosis inducing factor, AIF)L8=dbbROSVL8DNA(mitochondrialDNA, mtDNA)?3lM,7AUmtDNAlMM1%hEsMbN,L8%=0(Ca2+ )1/o0,%=Ca2+i1TbL8sV?%NMDAs8,%Ca2+=,#L8=Ca2+dbP=Ca2+i6,bL8t
7、M(V?*%1b*a75=%*%(?%,?+GL8ATPbL8?3?yH,%ATP,iV?*%.bm1 L8ATPROS3#ROS(1Duckles.MolInterv, 2006, 6: 26 35)=aL8*d%h:h(Alzheimers disease, AD)a7A*d%hBtM-M1%hb5-t%hh3b#,VL8?pa?st%h?3*+bL8?ya%=ROS39FV?ADa7A%h?3?Z1yBbADB*|%h,hyx(amyloid B, AB)MM1bV,ABV*%,iTABY,L8?,V7YL8=ATP3bv8kV,ABVA*?3,7%*(VnL8?y,L8MaROS39F
8、,#b,ABL8?y*%#75=%9bM5?C, AD7F?3mtDNAA9F,mtDNAlMbM1, ADmtDNA5 bpq9F5,IL8IVmtDNAlMADh9H?C1bmtDNAb#,wV?L8=ROS9FAB1(Wallace.2005)b$77Hq/,L8*%1yb7?3*,Vn*a%*%rq, ATP3h7ROS39F,L8#?3M;HWF,L8?Bs,V?CL8n.CL8a%=ATPaROSA6,#%=bL8tMV*a%75=%?,7u*%a75=?y,7p7bi, AD7A*d%hh3d,-L8t%h?3?ZWyT1Esb#baI*T#3M1,o-?37Aq3b7o8=I-1%,?37A75%h#166#3SZ2010M413qA9FbhVI(estro-gen therapy, ET)?AAD?3,7?b8=a8k4UHq/,AB*a!yaL8OaV_O#%!a,I7F*%(AT 2, 3b-Xv1I*T,7,tT1: (1)F*%,9bL8VZYL8?,aATP,139Fb%BiCa2+)VAL8,VI
