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白细胞分化抗原36蛋白的功能及其偶联信号通路
发布时间:2020-01-04

  摘    要: 白细胞分化抗原36 (cluster of differentiation 36, CD36)是一种高度糖基化的单链跨膜蛋白,属B型清道夫受体。其功能较为广泛,不仅可以识别“异己”成分,诱发免疫应答,还参与多种生理、病理过程。CD36作为膜受体与其他膜蛋白和胞质蛋白组成不同的信号通路。CD36是TRL4的辅助受体,可识别病原体相关分子模式,级联NF-κB信号通路,在天然免疫过程发挥作用;作为修饰脂蛋白受体,级联MAPK通路,诱发无菌性炎症及脂代谢紊乱,并参与动脉粥样硬化病变;作为外源长链脂肪酸受体,通过AMPK/mTOR信号通路在能量代谢及脂质蓄积过程中发挥调控作用。该文综述了CD36的分子特征及其偶联相关信号通路在天然免疫和脂代谢等方面的作用与机制,展示CD36的多功能特点,为相关生物医学研究提供依据。

  关键词:赢发彩票代理 CD36; 信号通路; 炎症反应; 脂代谢;

  Abstract: The cluster of differentiation 36(CD36) is a highly glycosylated single-chain transmembrane protein belonging to the B type scavenger receptor. The CD36 not only identifies the “exotic”component to cause immune response, but also regulates a variety of physiological and pathological processes. As a TLR4 co-receptor, CD36 recognizes pathogen-associated molecular patterns to activate NF-κB signaling pathway, which regulates the natural immune process. As a modified lipoprotein receptor, CD36 induces aseptic inflammation and lipid metabolism disorders to promote the development of atherosclerotic lesions through MAPK pathway. As an exogenous longchain fatty acid receptor, CD36 regulates the energy metabolism and lipid accumulation through the AMPK/mTOR signaling pathway. In this paper, we reviewed the molecular characteristics of CD36 and its role and mechanism in natural immunity and lipid metabolism, providing a basis for better application in biomedicine.

  Keyword: CD36; signaling pathway; inflammation; lipid metabolism;

赢发彩票代理   RENLEIBAIXIBAOFENHUAKANGYUAN36(cluster of differentiation36,CD36)SHUYUBZUQINGDAOFUSHOUTIJIAZU(scavenger receptor class B,SR-B),SHIYIZHONGJUYOUTESHUJINGHUANJIEGOUDEDANLIANKUAMODANBAI,QINDUANHECDUANZHIJIECHAOXIANGBAOZHI,ZHONGDUANZEZAIBAOWAIXINGCHENGYIGEKEYIHEDUOZHONGPEITIJIEHEDEHUAN[1,2]。QINGDAOFUSHOUTISHIBrownHEGoldsteinTUANDUIYU20SHIJI70NIANDAIZAIYANJIUJUSHIXIBAOBIAOMIANYIXIANHUADIMIDUZHIDANBAI(acetyl-LDL)SHOUTIGUOCHENGZHONGFAXIANDE[3],XINGCHENGYIGEKUAMOSHOUTICHAOJIAZU,JUYOUGUANGFANDEPEITISHIBIEWEIDIAN,SHIYIZHONGDUOGONGNENGSHOUTI。ZHIHOU,DUOZHONGQINGDAOFUSHOUTIBEIFAXIAN。1997NIAN,KriegerDENG[4]GENJUQIXULIEHEJIEGOUJIANYIJIANGQIFENWEIBUTONGDEZU,TONGCHANGYIA~HMINGMING;HOUYOUGENJUQIJIEGOUHESHENGWUXUEGONGNENGFENWEIA~JGONG10GEZU[5,6]。2017NIAN5YUE,MEIGUONIAIDHENIHZUZHI5GEGUOJIADE15WEIZHUANJIAJIANGQINGDAOFUSHOUTIFENWEISR-A~SR-L 11GEZU,QIZHONGSR-CZUWEIKUNCHONGTEYOU,QITAWEIBURUDONGWUSUOYOU,QIZHONGSR-BZUSHIWEIYIJUYOUERCIKUAMOJIEGOUDELEIXING,BAOKUOSR-B1(SR-BIHUOCD36L1)、SR-B2(CD36)HESR-B3(LIMP2)[1,5,6,7]。

  1、 CD36基因及CD36蛋白的分子特征

  人类CD36基因位于第七号染色体长臂q11.2,由15个外显子组成,长32 kb[8],ORF为1 419 bp,编码472个氨基酸残基,预测蛋白相对分子质量为53 kD[9]。CD36是一种多功能膜蛋白,其相对分子质量取决于细胞类型及糖基化修饰,修饰后相对分子质量为78~88 kD不等[9,10]。另外,CD36还会受到其他类型的翻译后修饰,且修饰会影响其功能,如CD36 N-糖基化后,会增加多种细胞对脂肪酸的吸收及利用;在血小板中,CD36被磷酸化后,会抑制其对脂肪酸的摄取功能等[9]。如图1所示,该蛋白结构主要分为五个区域:羧基末端细胞质域(COOH-终端)、氨基末端细胞质域(NH2-终端)、两个跨膜区以及一个胞外结构域。其中COOH-终端包含2个棕榈酰化位点和2个泛素化位点,NH2-终端只包含2个棕榈酰化位点,而这些棕榈酰化的末端对CD36定位在膜脂质筏上有着关键的作用[11,12]。胞外结构域是一个高度糖基化的大型疏水颈环结构,它含有3对二硫键,10个糖基化位点,2个磷酸化位点,这些修饰位点可以与多种胞外细胞及非细胞物质相互作用,如病原微生物或病原微生物感染的细胞、氧化低密度脂蛋白(oxidized lowdensity lipoprotein,ox-LDL)、凋亡细胞(apoptotic cell)、血小板反应蛋白(thrombospondin)及长链脂肪酸(long chain fatty acid,LCFA)等[11,13,14,15]。CD36蛋白具有的这种能与多种配体结合的特殊胞外结构域(图1)预示了其可能具有多种功能。
 

白细胞分化抗原36蛋白的功能及其偶联信号通路
 

  2、 CD36蛋白的功能

  CD36DANBAIZAIJUSHIXIBAO、GUGEJIXIBAO、SHENXIBAO、XINJIXIBAO、XUEXIAOBANYIJIGANXIBAOZHONGJUNYOUBIAODA[9,12,15],KEYIDULISHIBIEHEJIEHEDUOGENEIYUANHUOWAIYUANXINGPEITI。QIZHUYAOBAOHANSANLEI:BINGYUANXIANGGUANFENZIMOSHI(pathogen-associated molecular patterns,PAMPs)、NEIYUANXINGYANSHENGWEIXIANFENZI(RUox-LDL)HELCFA[11]。DUOZHONGPEITIYUCD36XIANGHUZUOYONG,TONGGUOBAONEIXINHAOZHUANDAO,YINFADUOZHONGSHENGWUXUEXIAOYING。

  2.1、 CD36作为清道夫受体在先天免疫反应中发挥作用

赢发彩票代理   DANHE/JUSHIXIBAODUIBINGYUANWEISHENGWUDETUNSHIZUOYONGKEYIYINFAMIANYIFANYINGJIQINGCHUBINGYUANTI,ZHEIZHONGXIANTIANMIANYIFANYINGXUYAOXIBAOSHIBIEPAMPs,RUBIANMAODANBAI(flagellin)、TAIJUTANG(peptidoglycan)、ZHIDUOTANG(lipopolysaccharide,LPS)DENG。TONGSHI,TollYANGSHOUTI(Toll-like receptors,TLRs)、QINGDAOFUSHOUTIDENGSHISHIBIEZHEIXIEPAMPsDEDIANXINGMOSHISHIBIESHOUTI(pattern recognition receptors,PRRs)。QINGDAOFUSHOUTICD36NENGGOUSHIBIEDUOZHONGBINGYUANWEISHENGWUJIQIJIEGOU,BINGJIEDAOXIBAOTONGGUOTUNSHIZUOYONGLAIDIAOJIEJITIWENTAIHEMIANYIFANGYU。ZAIGUOYINGZHONG,croquemort(crq)SHUYUCD36JIAZUCHENGYUANZHIYI。TUBIANDEGUOYING(crqko)YUYESHENGXINGGUOYINGXIANGBI,NENGGOUNEIHUAXIJUNDANBUNENGCHEDISHAMIEXIJUN,ZUIZHONGDAOZHIXIJUNJILEI,JITIBINGBIAN。crqZAIGANZHIBINGYUANTISHANGYUTollHEIMD(immune deficiency)XINHAOTONGLUXIETONGXINGSHIGONGNENG,HUOHUADETollHEIMDKEJINYIBUJIHUOHEYINZIκB(NF-κB)LEIZHUANLUYINZIRelish,CONGERLIYUSUZHUFANGYUGANRANHENAISHOUBINGYUANJUN[16,17]。ZAIMIANYANGZHONG,TLR4/PI3KXINHAOTONGLUZESHITONGGUOJIHUOXIAYOUJIYINCD36DEBIAODA,JINERTIGAODANHEXIBAO/JUSHIXIBAODENIANFUNENGLI,CUSHIQICANYUXIJUNDENEIHUA,YIJIAQIANGMIANYIFANGYUNENGLI。CHULEJIAQIANGXIBAODENIANFUNENGLIWAI,CD36HAICANYUJIDONGDANBAIGUJIADEZHONGPAI,JIAQIANGXIBAODETUNSHINENGLI[18],CONGERZAIDANHE/JUSHIXIBAODUIBINGYUANWEISHENGWUDENIANFU、NEIHUAYIJIQINGCHUZHONGFAHUIZHONGYAOZUOYONG。

  图1 CD36蛋白的结构示意图
图1 CD36蛋白的结构示意图

赢发彩票代理   CD36BUJINZUOWEIJUSHIXIBAOMOSHISHIBIESHOUTI,JIEDAOTUNSHIHEXIAOCHUWAILAIBINGYUANTI,HAIKEYISHIBIENEIYUANXINGPEITI,RUDIAOWANGHEHUAISIXIBAO、ox-LDLDENG。YONGXIBAODUXINGHUAISIYINZI1(cytotoxic necrotizing factor 1,CNF1)CHULIXIAOSHUJUSHIXIBAOFAXIAN,CNF1SHOUXIANTONGGUOJIHUORho GTPMEICdc42,JIANGDICD36SHANGYOUZHUANLUYINZILXRβHEC/EBPαDEBIAODALAIJIANRUODUIQIQIDONGZIDEMUJI,YIXIADIAOCD36BIAODA,ZUIZHONGZHISHIXIJUNDIDUHEZHONGXINGLIXIBAOZENGJIA,DAOZHIJIXINGNIAOLUGANRANQIJIANDEYANZHONGYANZHENGFANYING[13]。XINJIGENGSAIHOU,CD36HAIJIEDAOHESHOUTI(Nr4a1)YILAIXINGYOUDAOTUNSHISHOUTI(Mertk)DEBIAODA,ZUIZHONGTONGGUOTUNSHIZUOYONGQINGCHUHUAISIDEXINJIXIBAOLAIKONGZHIZAOQIGENGSAIMIANJIJIYANZHENGFANYING,BINGJINXINGXINZANGXIUFU[19]。CIWAI,ZAIDONGMAIZHOUYANGYINGHUAZHONG,ox-LDLYUCD36XIANGHUZUOYONGHUIJIHUOJUSHIXIBAONLRP3YANXINGXIAOTIJIDUOZHONGCUYANXINGXIBAOYINZIBIAODA,YOUFAWUJUNXINGYANZHENG[15],ERYANZHENGZEBEIRENWEISHIXINGCHENGDONGMAIZHOUYANGYINGHUABANKUAIDEZHUYAOYUANYINZHIYI。YINCI,ZONGSHANGSUOSHU,CD36YUBUTONGPEITIDEXIANGHUZUOYONGKENENGCHUFABUTONGLEIXINGDEYANZHENGFANYING,ZHEIXIANSHILECD36ZAIWEICHIMIANYIWENTAIZHONGDEZHONGYAOXING。

  2.2、 CD36作为脂蛋白受体参与动脉粥样硬化的形成

  20SHIJI70NIANDAI,GoldsteinTUANDUIZAISHIYANZHONGFAXIAN,QINGDAOFUSHOUTIHUISHEQUox-LDLBINGJIEDAOJUSHIXIBAOXINGCHENGPAOMOXIBAO,JINERYINQIJITIBINGBIAN,RUDONGMAIZHOUYANGYINGHUA[3]。ZICI,CD36YUZHIDANBAIZHIJIANZUOYONGGUANXISHOUDAOGUANZHU。2018NIAN,YazganDENG[14]ZHENGMINGWAIZHOUXUEDANHEXIBAOXIANGDONGMAIBIJINRUNBINGSHEQUox-LDLHOU,CD36DEBIAODALIANGSHENGGAO,ERQIECD36BUSHOUFUFANKUIDIAOJIE,HUIJIXUNEITUNox-LDL,JIASUXIBAOPAOMOHUA,TONGSHI,GUOYANGHUAWUMEIZENGZHIHUOHUASHOUTIγ(peroxisome proliferator-activated receptor-γ,PPARγ)HUOHEHONGXUEQIUXIANGGUANYINZI2(nuclear erythroid-related factor 2,Nrf2)BEIJIHUO,HUIJINYIBUCUJINCD36DEBIAODA,ZUIZHONGDAOZHIDONGMAIZHOUYANGYINGHUADEXINGCHENG[20,21]。

  ZHANGLIANFEIBIANMARNA(long non-coding RNA,lncRNA)YESHICANYUCD36SHEQUZHIDANBAIGUOCHENGZHONGDEYILEIZHONGYAODIAOJIEYINZI。ZAIRENJUSHIXIBAOZHONGQIAOJIANlncRNA NEAT1HEHOTAIRDEBIAODA,SHIDETAMENFENBIETONGGUOBAXIANGDIAOJIEmiR-128、miR-330-5pYIZHICD36BIAODAHEPAOMOXIBAOXINGCHENG,ERGUOBIAODAZEXIANSHILEXIANGFANDEJIEGUO[22,23]。WANQUANCHENMOCD36BIAODAYEHUIYINQIXUEGUANBINGBIAN[24]。YINCI,KEYITUICECD36ZAIJITIZHONGYINGGAICUNZAIYIGEHAIWEIBEIFAXIANDAODEZUIJIABIAODAZHI。ZHONGSUOZHOUZHI,JIESHICD36YUZHIDANBAIZHIJIANMIQIEDEXIANGHUZUOYONGGUANXIYOULIYUNONGQINGCHUCD36YUXUEGUANBINGBIANGUOCHENGDELIANXI。YINCI,ZAIZHUANLUSHUIPINGKONGZHICD36JIYINBIAODAHEZHUANLUHOUSHUIPINGKONGZHICD36DANBAILEIJIYUJIANGJIEHUISHILIANGTIAOFANGZHIDONGMAIZHOUYANGYINGHUADEYOUXIAOCAOKONGTUJING[25,26]。

  2.3、 CD36作为外源长链脂肪酸受体和转运蛋白在脂代谢中发挥作用

赢发彩票代理   CD36CHULEXINGSHIQI“QINGDAOFU”GONGNENGWAI,HAIZUOWEILCFADESHOUTIHEZHUANYUNQIZAIZHIDAIXIEZHONGQIZHONGYAOZUOYONG。20SHIJI90NIANDAI,KEXUEJIAMENFAXIANBINGKELONGLEYUZHIFANGXIBAOSHEQUZHIFANGSUANYOUGUANDEDANBAIZHI,JIANGQIJIANDINGWEIDUOGONGNENGMODANBAICD36[27]。SUIHOU,ZAI2005NIANSHI,LaugeretteDENG[28]ZAICIZHENGMINGLECD36YUZHIWEIJUEGANSHOUXIANGGUANLIAN。FEIPANGDASHUCD36QIAOCHUHOUBUZAIPIANAIFUHANLCFADERONGYE,TONGSHIQIXIAOHUAYEDEXINGZHIHEFENMILIANGYECHANSHENGLEBIANHUA[29]。ZAIHUANYOUGAOZHIXUEZHENGDETANGNIAOBINGSHENBINGHUANZHEDESHENZUZHIZHONGKEJIANCECHUCD36DEBIAODALIANGZENGJIA。YONGZONGLVSUANCHULIZUXIBAOHOUFAXIANCD36SHANGDIAOBIAODABINGCUJINQIZAIZUXIBAOZHONGCONGXIBAOZHIZHUANYUNZHIZHIMO,JINERYOUDAOZHIZHIJILEI、ROSCHANSHENGHEXIBAODIAOWANG,YOUFASHENBING[30]。GAOSHUIPINGPUTAOTANGTONGGUOSHANGDIAOAKT-PPARγDESHUIPING,CUJINCD36BIAODA,YIZENGJIASHENXIAOGUANXIBAODUIYOULIZHIFANGSUANDESHEQU,CONGERJIAJUXIBAOZHONGDEZHIZHICHENJIJICUJINTANGNIAOBINGSHENBINGDEFAZHAN[20],ZHEIXIEYANJIUCHENGGUODOUYOULIDISHUOMINGLECD36DUIZHIFANGSUANSHEQUJIZHIDAIXIEGUOCHENGDEZHONGYAOXING。CD36BAOWAIJIEHEYUDE127~279ANJISUANXULIEBEIRENWEISHILCFADEJIEHEWEIDIAN。RUCD36DEBUKENIYIZHIJIN-YOUXIANJILIUDAIHUPOXIANYAAN(sulfo-N-succinimidyloleate,SSO),TONGGUOJIEHELys164WEIDIANGAIBIANCD36DANBAIGOUXIANGCONGERXIANZHEJIANGDIYIXIANXIBAODUIZHIFANGSUANDESHEQUJIZHIZHIJIJU[31]。LCFASHINENGLIANGCHANSHENGDEZHONGYAODIWU,CD36HAIKEYICUJINLCFAZAIZHIFANGXIBAO、GANXIBAO、XINZANGHEGUGEJIXIBAOZHONGDEYIWEI[11]。YINCI,CD36BEIRENWEISHIZHILEIHEZHIFANGSUANDESHOUTI,BINGZAIXINCHENDAIXIEZONGHEZHENGZHONGQIZHONGYAOZUOYONG。ZAOQIRENWEICD36SHIZHUANYUNZHIFANGSUANSUOBIXUDE,DANYINWEIZAIDUOZHONGXIBAOZHONGBINGBUNENGQUEDINGCD36DUILCFADEYIWEIGONGNENG,ZHEIYIJIELUNHAIYOUDAIJINYIBUQUEREN[32],DANCD36ZUOWEIWAIYUANLCFASHOUTI,JINERCUJINZHIZHIHECHENGDEGONGNENGZHENGZAIYINQIYANJIUZHEDEZHUYI。

  2.4、 CD36的其他功能

  LINGYOUYANJIUBIAOMING,CD36HAIKEYIYINGXIANGZISHI、YANGHUAYINGJIDENGGUOCHENG。ZAIAtg5(YIZHONGGUANJIANDEZISHIJIYIN)QUEXIANDESHUTUZHUANGXIBAOZHONG,CD36BIAODASHENGGAO,BINGXIANSHICHUGUODUODEZHIZHIJILEI[33]。ZAIHepG2HEHuh7XIBAOZHONGGUOBIAODACD36KEYIYIZHIZISHI;ERQIAOCHUCD36HUILINSUANHUAunc-51YANGZISHIJIHUOJIMEI1(unc-51 like autophagy activating kinase 1,ULK1)HEZISHIXIANGGUANDANBAIBeclin1,CONGERTIGAOZHIDIZISHIJIANGJIE、ZHIZHIGUOYANGHUAJIβ-YANGHUADEXIAOLV,YOUXIAOGAISHANZHIZHIJILEI[34]。LINGWAI,ZHIFANGSUANHAIKEYITONGGUOCD36YOUDAOROSCHANSHENG,RULCFATONGGUOCD36SHANGDIAOYANGHUAYINGJICUJINGANXIBAOHUOHUA[35];ZONGLVSUANTONGGUOCD36YOUDAOZUXIBAOZHIZHISHEQU、ROSCHANSHENGHEXIBAODIAOWANGDENG[30]。DANSHI,CD36CANYUZHIFANGSUANYOUDAOROSCHANSHENGDEQUEQIEZUOYONGJIZHIHEDIAOJIEGUOCHENGXIANZAISHANGBUQINGCHU,SHIDANGXIAZHENGZAIJINXINGDEYANJIUZHUTI。

  3、 CD36及其偶联的信号通路

  3.1、 CD36与TLRs信号通路

赢发彩票代理   TollYANGSHOUTI(TLRs)SHIPRRsJIAZUCHENGYUAN,ZAISHENGWUZHONGGAODUBAOSHOU。TLR4SHIZAIRENLEIZHONGFAXIANDEDIYIGETLRsXIANGGUANDANBAI,BIAODAZAIXIBAOMOBIAOMIAN[36],SHILPSDEGUANJIANSHOUTI。MUQIANYANJIUFAXIAN,CD36KEYIFUZHUTLR4XIETONGJIEDAOLPSCIJIXINHAO,DIAOJIESUIYANGFENHUAYINZI88(myeloid differentiation factor 88,MyD88)HEZHONGLIUHUAISIYINZISHOUTIXIANGGUANYINZI6(TNF receptor-associated factor 6,TRAF6),JIHUONF-κBHEJIHUODANBAI1(activator protein-1,AP-1)DENGZHUANLUYINZI,CONGERYOUDAOXIBAOCHANSHENGIL-1β、IL-6、IL-8、TNF-αDENGYANZHENGYINZI[12]。CIWAI,TLR4HAIKEYIJIHUOPI3K(phospholinositide 3-kinase),XINGCHENGTLR4-PI3KXINHAOTONGLU,SHANGDIAOCD36JIYINBIAODA,FANGUOLAIHUOHUACD36-TLR4FUHEWU[18],ZUIZHONG,XIBAOHUIQIDONGYIXILIEMIANYIYANZHENGFANYING,QINGCHURUQINDEBINGYUANWEISHENGWU。

  3.2、 CD36与MAPK信号通路

赢发彩票代理   SILIEYUANHUOHUADANBAIJIMEITONGLU(mitogen-activated protein kinase,MAPK)CANYUXIBAOZHONGDUOZHONGSHENGLIBINGLIGUOCHENGBINGFAHUIZHONGYAOZUOYONG。MAPKJIAZUZHONGBAOHANDUOZHONGBUTONGDEDANBAI,QIZHONGBAOWAIDIAOJIEDANBAIJIMEI(extracellular regulated protein kinase,ERK)、c-JunANJIMODUANJIMEI(c-Jun N-terminal kinase,JNK)HEp38SHIYANJIUZUIGUANGFANHEZUIZHONGYAODEDANBAIJIMEI,QILINSUANHUASHUIPINGJUEDINGLEQIHUOXINGCHENGDU。XUEZHIYICHANGQINGKUANGXIA,CD36KEYITONGGUOJIHUOYANGHUAHAIYUANMINGANDEXINHAOFENZI,RUERK5,CUJINXUESHUANXINGCHENG,QIJIZHISHIox-LDL-CD36TONGGUOXINHAOFENZISrcJIMEI、ERK5HUOHUACUJINCUNINGJILINZHIXIANSIANSUAN(phosphatidylserine,PSer)ZAIXUEXIAOBANBIAOMIANBAOLU,SUIHOUNINGXUEMEIYUANFUHEWUBEIMUJI,CHANSHENGXIANWEIDANBAI,ZUIZHONGCUJINDONGMAIXUESHUANXINGCHENG[37,38]。2016NIAN,WangDENG[39]ZAIXUEYEZHONGFAXIANLEox-LDL/CRP/β2GP1FUHEWU,QIBIox-LDLGENGJUWENDINGXING。GAIFUHEWUTONGGUOTIGAOCD36、ATPJIEHEHEDANBAIABCA1DENGZHUANLUSHUIPINGJIIL-1β、IL-6、TNF-αDEBIAODA,JIHUOp38 MAPK/NF-κBXINHAOTONGLU,YOUDAOJUSHIXIBAODEZHIZHIJIJUHEYANZHENGFANYING。LINGYOUYANJIUBIAOMING,GONGNENGSHIDIAO/CUYANDEGAOMIDUZHIDANBAI(dysfunctional/proinflammatory HDL,piHDL)KEYIYOUDAOPPARγHENrf2BIAODA,SHIBAOLUYUpiHDLDEJUSHIXIBAODALIANGBIAODACD36DANBAIBINGTONGSHIJIHUOMAPK ERKHENF-κBXINHAOTONGLU[40],YIZHIXINGCHENGPAOMOXIBAO。CIWAI,MEIXIUSHIDIMIDUZHIDANBAI(enzymatically modified LDL,e-LDL)YOUDAOCD36JIABCA1BIAODA,BINGXIANZHETIGAOIL-8HEJUSHIXIBAOYANXINGDANBAI-1β/QUHUAYINZI(MIP-1β/CCL4)DEFENMI,TONGSHIJIHUOp38 MAPKXINHAOTONGLUYINFAYANZHONGDEYANZHENGFANYING[41]。CD36KEYIHEDUOZHONGXIUSHIZHIDANBAIZUOYONG,DAOZHIZHIDAIXIEWENLUANHEYANZHENGFANYINGBINGYOUFAXINXUEGUANJIBING[37,38,39,40]。

  3.3、 CD36与FAK信号通路

赢发彩票代理   NIANFUBANJIMEI(focal adhesion kinase,FAK)SHIYIZHONGBAOZHIFEISHOUTILAOANSUANJIMEI,NDUANFERM(F for 4.1protein,E for ezrin,R for radixin and M for moesin)QUYUSHIHEXINGONGNENGYU,TONGSHI,TAYESHIZHENGHESUXINHAOTONGLULIYIGEZHONGYAODEDIAOJIEYINZI,YUXIBAOQIANYI、NIANFUHEQINXIYOUGUAN。1992NIAN,SHOUCIFAXIANFAKXIANGGUANDANBAISrcJIAZUJIMEI(RULyn、Fyn)[42],QISHICD36YUFAKLIANJIEDEZHONGJIANFENZI,GOUCHENGCD36/Lyn/FAKHUOCD36/Fyn/FAKXINHAOTONGLU。DANGJUSHIXIBAOSHOUDAOWAIJIECIJISHI(RUox-LDL),CD36HUIYOUDAOXINHAOJILIAN,DAOZHITEYIXINGSrcJIMEI(LIRULynHUOFyn)DEHUOHUA,BINGJIHUOFAK[43]。CD36/FAKXINHAOTONGLUDEJIHUOJINYIBUCUJINLEPAOMOXIBAODEXINGCHENGYUKUOZENG,TONGSHIHUOHUAHOUDEFAKHAIHUIJINYIBUJIHUOJIDONGDANBAIXIANGGUANDANBAI2/3(Arp2/3)FUHEWU,YINGXIANGJIDONGDANBAIJUHE,YIZHIJUSHIXIBAOQIANYIZHIQUYULINBAJIE,NEIMOZHONGDEPAOMOXIBAOBEIBUHUO,DAOZHIYANZHENGJIXUEGUANSUNSHANGDEXINGCHENG[44,45]。

  3.4、 CD36与mTOR信号通路

  BURUDONGWULEIPAMEISUBADANBAI(mammalian target of rapamycin,mTOR)SHIFEIDIANXINGXINGSer/ThrJIMEIDANBAI,SHUPIKK(phosphatidylinositol kinase-related kinase)CHAOJIAZU,ZAIDIAOKONGXIBAOZENGZHIGUOCHENGZHONGFAHUIHEXINZUOYONG。m TORXINGCHENGLIANGZHONGBUTONGDEGONGNENGFUHEWU,m TORC1HEm TORC2。QIZHONGm TORC1DUITEYIXINGYIZHIJIrapamycinMINGAN,ERmTORC2BUMINGAN。YIDANSHOUDAOYINGYANGHUOYANZHENGYINZIXINHAOCIJI,mTORC1JIUHUIHUOHUAXIAYOUHETANGTIDANBAIS6JIMEI(ribosomal protein S6 kinase,S6Ks)、ZHENHEFANYIQISHIYINZI4EJIEHEDANBAI(eukaryotic initiation factor 4E-binding proteins,4E-BPs)、ZHENHEQISHIYINZI4E(eukaryotic initiation factor 4E,eIF4E),YINFAXINHAOJILIANFANYING,FAHUIGONGNENG。YETIGUOTANGBUCHONGJI(LFS)WEISHIXIAOSHUHOU,KEYIGUANCHADAOGANZANGZHONGCD36、PPARγBIAODAJIGANZANGDANGUCHUNSHENGWUHECHENGZENGJIA,QIEBANSUIZHELFSYOUDAODEGANZANGmTORLINSUANHUA,ZUIZHONGDAOZHIGANZANGYIDAOSUXINHAOZHUANDAOQUEXIANHEQUANSHENYIDAOSUMINGANXINGJIANGDI[46]。RUANZHISUAN(palmitic acid,PA)CHULIRENGANAIXIBAOJIXIAOSHUGANZANGZUZHIKEYIJIHUOmTORXINHAOTONGLUJITIGAOCD36FANYIXIAOLV,ZUIZHONGYINQIZHIZHIXUJI[47]。YANZHENGYINGJIKEYITONGGUOJIHUOmTORXINHAOTONGLUTIGAOGANZANGCD36DEFANYIXIAOLV[48];XIANGFAN,mTORC1TEYIXINGYIZHIJILEIPAMEISUKEYIYIZHIGANZANGCD36DEFANYIXIAOLV,JIANQINGZHIFANGGAN[49]。ZHEIXIEJIEGUOJIESHILECD36HEmTORXINHAOTONGLUZAIZHIZHIDAIXIEZHONGDEZUOYONG。

  3.5、 CD36与AMPK通路

赢发彩票代理   AMP-HUOHUADANBAIJIMEI(AMP-activated protein kinase,AMPK)SHIYIZHONGGAODUBAOSHOUDEXIBAONEINENGLIANGZHUANGTAIDEZHUYAOCHUANGANQI。ZHIFANGSUAN(fatty acid,FA)NENGTONGGUOCD36JIHUOGANJIMEIB1(liver kinase B1,LKB1)JIEDAOAMPKLINSUANHUA。JIER,SHICD36CANYUFyn/LKB1/AMPKTONGLU,BINGYUZHEIXIEDANBAIXINGCHENGFUHEWULAIXINGSHIGONGNENG。RUTU2SUOSHI,ZAIDILIANGWAIYUANFAZUOYONGXIA,GAIFUHEWUTONGGUOFynZUZHILKB1YUAMPKJIECHU,YIZHIAMPKHUOHUA,CONGERSHIAMPKBAOCHIJINGXIZHUANGTAI。SUIZHEWAIYUANXINGFAZENGJIA,YUCD36JIEHEDEFAJIELIFyn,KONGJIANSHANGXUERUOQIDUILKB1DEJIEJINCONGERJIECHUZHEIZHONGYIZHIBINGSHILKB1LINSUANHUA,SUIHOULKB1BEICONGXIBAOHEMUJIDAOXIBAOZHIBINGFUJIHUOHUAAMPK[50],CONGERYINGXIANGFADESHEQUYUYANGHUA。SUIHOU,HUOHUADEAMPKHUIMUJIGENGDUODECD36ZAIMOSHANGDINGWEI[51,52],ZUIZHONGDAOZHIZHIZHIJILEI。

  4、 小结与展望

  ZONGSHANGSUOSHU,CD36DEBAOWAIJIEGOUYUHANYOUDUOGEJIEHEWEIDIAN,KEYIYUDUOZHONGPEITIXIANGJIEHE,ZHEIYEJUEDINGLEQIGONGNENGDEDUOYANGXING。CD36OULIANDEXINHAOTONGLUCANYUYANZHENGFANYINGHEZHIZHIDAIXIEDEJIZHIGUINAYUTU3。CD36FUZHUTLR4YIMyD88YILAIXINGTUJINGJIHUONF-κB,SHIJITICHANSHENGYANZHENGFANYING;DANGXIBAOSHOUDAOWAIJIECIJISHI(RUGELEIXIUSHIZHIDANBAI),CD36HUIYOUDAOXINHAOJILIAN,ZAOCHENGCD36/p38 MAPK、CD36/ERK MAPKDENGXINHAOTONGLUBEIJIHUO,ZUIZHONGYINQIZHIDAIXIEWENLUAN、YANZHENGFANYINGBINGYOUFAXINXUEGUANJIBING;CD36HAIKEYIJIHUOmTOR、AMPKXINHAOTONGLU,ZHENGSHILEQIZAINENGLIANGDAIXIEJIZHIZHILEIJIZHONGFAHUIZHONGYAOZUOYONG。

赢发彩票代理   CD36DEGONGNENGYANJIUZHUYAOJIZHONGZAIBURUDONGWUBINGYUANTISHIBIEHEFANGYU、WAIYUANZHIFANGSUANDESHEQUHEZHIDAIXIEDENG。JINNIANDEYANJIUBIAOMING,CHULE“QINGDAOFU”HEMOZHUANYUNQIGONGNENGWAI,CD36ZUOWEISHOUTIJIEDAOZHANGLIANZHIFANGSUANXINHAOCUJINXIBAONEIZHIHUAZUOYONGKENENGGENGWEIZHONGYAO,TAKEYITONGGUOTIGAOXIBAONEIZHIHUAXIAOLV,ERBUSHITONGGUOQIANGHUAZHUANYUNZUOYONGLAIJIAQIANGXIBAOWAIZHIFANGSUANDESHEQU。CD36KENENGTONGGUOYOUFAOULIANDEXIBAOXINHAOZHUANDAOGUOCHENG,CUJINZHIFANGSUANDEZHIHUA,DANJUTIFENZIJIZHIHAIBUQINGCHU。CIWAI,CD36CANYUDIAOKONGDEDAIXIEWENLUANXIANGGUANJIBINGCHANGBANSUIZHEYANZHONGDEYANZHENGFANYING,ERZHEZHIJIANXIANGHUZUOYONGFENZIJIZHIHAIWEIBEIWANQUANJIESHI。SHIFOUKEYITONGGUOKANGYANZHILIAOGAISHANJITIDAIXIEZHUANGTAI,HUOKONGZHIYICHANGDEZHIZHINEIHUAFANGUOLAIJIANQINGMANXINGYANZHENGFANYING,CONGERFANGZHIDAIXIEZONGHEZHENG,SHANGXUJINYIBUYANJIU。DANGRAN,CD36BIAODAYUZHIDEWENTIYESHIZHIDEZHONGDIANTANSUODEFANGXIANG。

  图2 脂肪酸对CD36-Fyn-LKB1-AMPK复合物的作用
图2 脂肪酸对CD36-Fyn-LKB1-AMPK复合物的作用

  图3 CD36在炎症反应和脂质代谢中发挥作用
图3 CD36在炎症反应和脂质代谢中发挥作用

  参考文献

  [1] Neculai D, Schwake M, Ravichandran M, et al. Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36. Nature, 2013, 504:172-6
  [2] P?ociennikowska A, Hromada-Judycka A, Borz?cka K, et al. Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling. Cell Mol Life Sci, 2015, 72:557-81
  [3] Goldstein JL, Ho YK, Basu SK, et al. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA, 1979, 76:333-7
  [4] Krieger M. The other side of scavenger receptors:pattern recognition for host defense. Curr Opin Lipidol, 1997, 8:275-80
  [5] Zani IA, Stephen SL, Mughal NA, et al. Scavenger receptor structure and function in health and disease.Cells, 2015, 4:178-201
  [6] Prabhudas M, Bowdish D, Drickamer K, et al. Standardizing scavenger receptor nomenclature. J Immunol, 2014, 192:1997-2006
  [7] PrabhuDas MR, Baldwin CL, Bollyky PL, et al. A consensus definitive classification of scavenger receptors and their roles in health and disease. J Immunol, 2017,198:3775-89
  [8] Hoosdally SJ, Andress EJ, Wooding C, et al. The human scavenger receptor CD36:glycosylation status and its role in trafficking and function. J Biol Chem, 2009, 284:16277-88
  [9] Luiken JJ, Chanda D, Nabben M, et al. Post-translational modifications of CD36(SR-B2):implications for regulation of myocellular fatty acid uptake. Biochim Biophys Acta, 2016, 1862:2253-8
  [10] Armesilla AL, Vega MA. Structural organization of the gene for human CD36 glycoprotein. J Biol Chem, 1994,269:18985-91
  [11] Yang X, Okamura DM, Lu X, et al. CD36 in chronic kidney disease:novel insights and therapeutic opportunities.Nat Rev Nephrol, 2017, 13:769-81
  [12] Cao D, Luo J, Chen D, et al. CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells. Sci Rep,2016, 6:23132
  [13] Yang H, Li Q, Wang C, et al. Cytotoxic necrotizing factor1 downregulates CD36 transcription in macrophages to induce inflammation during acute urinary tract infections.Front Immunol, 2018, 9:1987
  [14] Yazgan B, Sozen E, Karademir B, et al. CD36 expression in peripheral blood mononuclear cells reflects the onset of atherosclerosis. Biofactors, 2018, 44:588-96
  [15] Du X, Jiang S, Zeng X, et al. Air pollution is associated with the development of atherosclerosis via the cooperation of CD36 and NLRP3 inflammasome in ApoE-/-mice.Toxicol Lett, 2018, 290:123-32
  [16] Guillou A, Troha K, Wang H, et al. The Drosophila CD36homologue croquemort is required to maintain immune and gut homeostasis during development and aging. PLoS Pathog, 2016, 12:e1005961
  [17] Zhai Z, Huang X, Yin Y. Beyond immunity:the Imd pathway as a coordinator of host defense, organismal physiology and behavior. Dev Comp Immunol, 2018, 83:51-9
  [18] Wang S, Deng S, Cao Y, et al. Overexpression of Toll-like receptor 4 contributes to phagocytosis of Salmonella enterica serovar Typhimurium via phosphoinositide3-kinase signaling in sheep. Cell Physiol Biochem, 2018,49:662-77
  [19] Dehn S, Thorp EB. Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1-dependent mechanisms of cardiac repair. FASEB J,2018, 32:254-64
  [20] Feng L, Gu C, Li Y, et al. High glucose promotes CD36expression by upregulating peroxisome proliferatoractivated receptorγlevels to exacerbate lipid deposition in renal tubular cells. Biomed Res Int, 2017, 2017:1414070
  [21] Chistiakov DA, Bobryshev YV, Orekhov AN. Macrophagemediated cholesterol handling in atherosclerosis. J Cell Mol Med, 2016, 20:17-28
  [22] Chen DD, Hui LL, Zhang XC, et al. NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128. J Cell Biochem,2019, 120:2493-501
  [23] Liu J, Huang GQ, Ke ZP. Silence of long intergenic noncoding RNA HOTAIR ameliorates oxidative stress and inflammation response in ox-LDL-treated human macrophages by upregulating miR-330-5p. J Cell Physiol,2019, 234:5134-42
  [24] Choromańska B, My?liwiec P, Choromańska K, et al. The role of CD36 receptor in the pathogenesis of atherosclerosis.Adv Clin Exp Med, 2017, 26:717-22
  [25] Wang C, Xu W, Liang M, et al. CTRP13 inhibits atherosclerosis via auto phagylysosome-dependent degradation of CD36.FASEB J, 2019, 33:2290-300
  [26] Tang Y, Wu H, Shao B, et al. Celosins inhibit atherosclerosis in ApoE-/-mice and promote autophagy flow. J Ethnopharmacol,2018, 215:74-82
  [27] Grimaldi PA, Knobel SM, Whitesell RR. Induction of aP2gene expression by nonmetabolized long-chain fatty acids.Proc Natl Acad Sci USA, 1992, 89:10930-4
  [28] Laugerette F, Passillydegrace P, Patris B, et al. CD36involvement in orosensory detection of dietary lipids,spontaneous fat preference, and digestive secretions. J Clin Invest, 2005, 115:3177-84
  [29] Douglas Braymer H, Zachary H, Schreiber AL, et al.Lingual CD36 and nutritional status differentially regulate fat preference in obesity-prone and obesity-resistant rats.Physiol Behav, 2017, 174:120-7
  [30] Hua W, Huang HZ, Tan LT, et al. CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress.PLoS One, 2015, 10:e0127507
  [31] Glatz JF, Luiken JJ. From fat to FAT(CD36/SR-B2):understanding the regulation of cellular fatty acid uptake.Biochimie, 2017, 136:21-6
  [32] Jay AG, Hamilton JA. The enigmatic membrane fatty acid transporter CD36:new insights into fatty acid binding and their effects on uptake of oxidized LDL. PLEFA, 2018,138:64-70
  [33] Oh DS, Lee HK. Autophagy protein ATG5 regulates CD36expression and anti-tumor MHC class II antigen presentation in dendritic cells. Autophagy, 2019, 22:1-16
  [34] Li Y, Yang P, Zhao L, et al. CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway. J Lipid Res, 2019, 60:844-55
  [35] Liu J, Yang P, Zuo G, et al. Long-chain fatty acid activates hepatocytes through CD36 mediated oxidative stress.Lipids Health Dis, 2018, 17:153
  [36] Medzhitov R, Preston-Hurlburt PP, Janeway CA JR. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature, 1997, 388:394-7
  [37] Yang M, Kholmukhamedov A, Schulte ML, et al. Platelet CD36 signaling through ERK5 promotes caspasedependent procoagulant activity and fibrin deposition in vivo. Blood Adv, 2018, 2:2848-61
  [38] Yang M, Cooley BC, Li W, et al. Platelet CD36 promotes thrombosis by activating redox sensor ERK5 in hyperlipidemic conditions. Blood, 2017, 129:2917-27
  [39] Wang J, Feng MJ, Zhang R, et al. C-reactive protein/oxidized low density lipoprotein/β2-glycoprotein I complexes induce lipid accumulation and inflammatory reaction in macrophages via p38/mitogen-activated protein kinase and nuclear factor-κB signaling pathways. Mol Med Rep, 2016, 14:3490-8
  [40] Sini S, Deepa D, Harikrishnan S, et al. High-density lipoprotein from subjects with coronary artery disease promotes macrophage foam cell formation:role of scavenger receptor CD36 and ERK/MAPK signaling. Mol Cell Biochem, 2017, 427:23-34
  [41] Cheng F, Twardowski L, Fehr S, et al. Selective p38αMAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes:implications for atherosclerosis. FASEB J, 2017, 31:674-86
  [42] Schaller MD, Borgman CA, Cobb BS, et al. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA, 1992, 89:5192-6
  [43] Kong DB, Chen F, Sima N. Focal adhesion kinases crucially regulate TGFβ-induced migration and invasion of bladder cancer cells via Src kinase and E-cadherin.Onco Targets Ther, 2017, 10:1783-92
  [44] Xu S, Li L, Yan J, et al. CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration. Biomed Pharmacother, 2018, 97:1020-31
  [45] Nimgulkar C, Ghosh S, Sankar AB, et al. Combination of spices and herbal extract restores macrophage foam cell migration and abrogates the athero-inflammatory signalling cascade of atherogenesis. Vascul Pharmacol,2015, 72:53-63
  [46] Zhao L, Zhang C, Luo X, et al. CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis. J Hepatol,2018, 69:705-17
  [47]王川.高脂及炎症状态激活mTOR信号通路导致肝脏CD36翻译效率升高[D].重庆:重庆医科大学, 2014
  [48] Wang C, Hu L, Zhao L, et al. Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway. PLoS One,2014, 9:e103071
  [49] Wang C, Yan Y, Hu L, et al. Rapamycin-mediated CD36translational suppression contributes to alleviation of hepatic steatosis. Biochem Biophys Res Commun, 2014,447:57-63
  [50] Samovski D, Sun J, Pietka T, et al. Regulation of AMPK activation by CD36 links fatty acid uptake toβ-oxidation.Diabetes, 2015, 64:353-9
  [51] Zhao L, Zhang C, Luo X, et al. CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis. J Hepatol,2018, 69:705-17
  [52] Choi YJ, Lee KY, Jung SH, et al. Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice.Toxicol Appl Pharmacol, 2017, 316:74-82

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