河北快3

您好,欢迎来到四川海恩贝生物科技有限公司设为河北快3|加入收藏|联系我们
联系我们

DIZHI:CHENGDOUSHIWUHOUQUWUHOUXINCHENGGUANWEIHUIWUKEDONGERLU11HAO7DONG4LOU7-1HAO

DIANHUA:028-85305096

河北快3
您的当前位置:河北快3 > 河北快3 > 河北快3

Nature:FAXIANXINLISHUAIJIEDEZUIKUIHUOSHOU

发布作者:管理员 发布时间:2015-03-20 14:08:04 点击率:

最近,来自约翰霍普金斯医学院和其他机构的科学家,利用实验室动物和人类心肌细胞,发现了“一个细胞信号故障触发心力衰竭”谜团背后长期寻求的“罪魁祸首”。心力衰竭影响将近600百万美国人和全世界2300万人,特点是逐步衰弱和心肌硬化以及器官泵血能力的逐渐丧失。

XIANGGUANYANJIUJIEGUOFABIAOZAISANYUESHIBARIDE《ZIRAN》ZAZHI(Nature),BIAOMINGYIZHONGMEI(CHENGWEIPDE-9)HUIGANRAOSHENTIXIAOCHUXINZANGYALISUOBIXUDEDEZIRAN“ZHIDONG”XITONG。SHIYANJIEGUOBIAOMING,ZHEIZHONGMEIHUITONGGUOTUNSHIYIGEXINHAOFENZIcGMPERZAOCHENGSHANGHAI,cGMPTONGCHANGKECIJIXINZANGBAOHUXINGDANBAI(CHENGWEIPKG)DESHENGCHAN,ZHEIZHONGDANBAIYIZHIKEBAOHUXINJIMIANSHOUJIBINGDAOZHIDEYINGLIPOHUAI,RUZHANGQIGAOXUEYA。

YANJIURENYUANSHUO,PDE-9ZIRANCUNZAIYUCHANGDAO、SHENZANGHEDANAOZHONG,SHISHENJINGTUIXINGXINGJIBING(RUAERCIHAIMOSHIZHENG)DE“TOUHAOXIANFAN”。DANSHIXINDEYANJIUBIAOMING,ZHEIZHONGMEIYECHUXIANZAIXINZANGXIBAOZHONG,BINGQIEZAIXINLISHUAIJIEBINGRENZHONGMINGXIANSHENGGAO,ZHEIBIAOMINGPDE-9SHIYIGEDUORENWUHUADE“ZUIFAN”,YESHIXINJISIWANGDEYIGEGUANJIANCUFAZHE。

WEILELEJIEZHEIZHONGMEIDEZUOYONG,KEXUEJIAMENLIYONG“XINZANGJIROUDEJIANKANGSHIYOULIANGZHONGDULIDEJIZHIHUOXINHAOZHUANDAOTONGLUBAOHU”DEZHISHI。TONGGUOLIANGZHONGBUTONGDEHUAXUEWUZHI——YIYANGHUADAN、XINNASUJIHUO,MEIGETONGLUDOUHUICHANSHENGcGMP,ZHEIFANGUOLAIYOUCIJIFEICHANGZHONGYAODEXINJIBAOHUYINZIPKG。YANJIURENYUANSHUO,DADUOSHUXINLISHUAIJIEBINGLISHIYOUYULIANGGETONGLUDEGUZHANGERYINFADE。

YUEHANHUOPUJINSIYIXUEYUANJIXINZANGHEXUEGUANYIXUEYANJIUSUOJIAOSHOUDavid KassBOSHISHUO:“ZHEILIANGGETONGLUDECUNZAIXIANGHUZHONGDIE,DANJUYOUBUTONGDEGONGNENGSHIDAZIRANDEBAODAN——YIZHONGZIDONGFANGGUZHANGZHUANGZHI,YIQUEBAORUGUOYIGETONGLUFASHENGGUZHANG,LINGYIGETONGLUKEYIBUCHANGHEWEICHIXINJIGONGNENG。”

JINSHINIANQIAN,KassDAILINGDEYANJIUTUANDUIQUEDINGLEYINFAQIZHONGYIGEXINHAOTONGLUGUZHANGDEZUIKUIHUOSHOU——YIZHONGMINGWEIPDE-5DEMEI,ZHEIZHONGMEIYIZHIYEDAOZHIBOQIGONGNENGZHANGAI。ZINEIYIHOU,KEXUEJIAMENYIZHIZAIXUNZHAOYINQILINGWAIYIGETONGLUGUZHANGDEDIER“ZUIFAN”。GAIYANJIUXIAOZUSHUO:“PDE-9KENENGJIUSHIWOMENZHANGQIXUNZHAODEZUIKUIHUOSHOU。”

BENWENSHOUXIYANJIUYUAN、YUEHANHUOPUJINSIYIXUEYUANXINZANGBINGXUEYANJIUZHULIDong Lee BOSHISHUO:“XIANGYIGEJUYOUDUOGEJIAOSEDEJUBENYIYANG,XINZANGJIROUGONGNENGSHIYOUJIZHONGDANBAIZHI、MEIHEJISUDEFUZADANWANQUANTONGBUDEXIANGHUZUOYONGZAOCHENGDE。WOMENDEYANJIUJIEGUOBIAOMING,JIUXIANGHUIJUZAIJUBENJIEWEIDELIANGGECIYAOQINGJIE,PDE-5HEPDE-9SHIDULIDECAOZUOZHE,MEIGEDOUDAOZHIXINZANGJIROUSUNSHANG,DANSHITONGGUOBUTONGSHOUDUANWANCHENGDE。”

KassXIANQIANDEYANJIUBIAOMING,PDE5JIUXIANGTAXINFAXIANDE“GONGFAN”PDE-9YIYANG,TONGGUOYIKAOXINZANGBAOHUXINGcGMPHEPKGERZAOCHENGSUNHAI。DANXINDEYANJIUJIEGUOJIESHILEYIGEZHONGYAODECHAYI——PDE-9DUIDIERXINHAOTONGLUCIJIDEcGMPXINGSHIYOUXINGQU。

KassSHUO,HUANJUHUASHUO,TAIDUODEPDE-9KETONGGUOJIAKUAIcGMPFENJIE,GANRAOLIANGGEXINZANGBAOHUXITONGZHONGDEDIERGE,ZHEIFANGUOLAIYOUJIANGDILEPKGDESHUIPING,SHIXINZANGXIBAORONGYICHUXIANGUZHANG,BINGQIEXINJIRONGYILIUXIABAHENHESUNSHANG。

GAIYANJIUXIAOZUHAIZHICHU,KENENGMASHANGHUICHUXIANZUDUANPDE-9HUOXINGDEXINLISHUAIJIELIAOFA,YIZHIPDE-9DEYAOWUYIJINGYONGYUAERCIHAIMOSHIBINGHUANZHECESHI。

ZAIMUQIANDEYANJIUZHONG,ZHEIZHONGPDE-9ZUZHIJIZAIXINLISHUAIJIEXIAOSHUZHONGBUJINTINGZHILEXINZANGJIROUKUODAHEBAHENXINGCHENG,ERQIETAMENJIHUKENIZHUANJIBINGDEYINGXIANG。

KassSHUO:“WOMENXIANGXIN,PDE-9DEFAXIAN,BAWOMENTUIXIANGLECHUANGJIANJINGQUELIAOFA(BADINGDIERTONGLU)HUOKAIFALIANHELIAOFA(BIMIANLIANGGETONGLUFASHENGGUZHANG)DEJIANDUAN。”

XINDEYANJIUJIEGUOKENENGDUIYUJINYIBANJUYOUTEBIEWANGUXINSHUAIDEHUANZHEGENGYOUYIYI,ZHEIZHONGXINSHUAISHIJUYOUBAOCUNSHEXUEFENSHUDEXINLISHUAIJIE,SHIYIZHONGNAIZHILIAOXINGDEXINSHUAI,HUANZHEXINZANGSIHUNENGZHENGCHANGCHOUDONG,DANSHISHISHANGYIJINGSHANGHENLEILEIHEYINGHUA。YANJIURENYUANZHICHU,CONGZHEIZHONGJIBINGHUANZHEHUODEDEXINZANGXIBAO,QIPDE-9SHUIPINGBIZHENGCHANGXINZANGGAOCHULIUBEI,CONGERBIAOMINGZHEIZHONGXINGSHIDEJIBINGHUANZHEYOUGENGSHAODEXINZANGBAOHUXINGPKG。

ZAIYIZUSHIYANZHONG,YANJIURENYUANYONGHUAXUEFANGFACIJIRENLEIXINZANGXIBAOHELAIZIXINSHENGXIAOSHUDEXIBAO,YIMOFANGXINLISHUAIJIEDEXIAOGUO。XIBAOPENGZHANGCHAOCHUQIZHENGCHANGDEDAXIAO,DANSHIDANGYONGPDE-9JIEDUJIZHILIAOSHI,XIBAOHUIFUDAOJIEJINYUZHENGCHANG。

ZAILINGYIGECESHIZHONG,KEXUEJIAMENZHIBEILEZHUANXIAOSHU,TAMENBUNENGZHIZAOPDE-9,BINGJIANGTAMENDEXINZANGXIBAOHEQIGUANGONGNENGYUJUYOUWANZHENGPDE-9JIYINDEXIAOSHUJINXINGDUIBI。YUJUYOUWANZHENGPDE-9DEXIAOSHUXIBAOXIANGBI,QUEFAPDE-9DEXIAOSHUXIBAOJUYOUGENGGAODEcGMPSHUIPING。JIEXIALAI,LIANGZUXIAOSHUJIESHOULEZHUDONGMAISHOUSHUSUOXIAO,ZHIZAIJIXINZANGCHANSHENGEWAIDEGONGZUOLIANG,CONGERYOUDAOXINLISHUAIJIE。QUEFAPDE-9JIYINDEXIAOSHUBIAOXIANYAOHAODEDUO。YUJUYOUWANZHENGPDE-9DEXIAOSHUXINZANGXIANGBI,TAMENDEXINZANGYOUGENGSHAODEBAHEN、JIROUZENGHOUHEKUOZHANG。

ZAIDISANGESHIYANZHONG,KEXUEJIAJIANGSHOUSHUYOUDAOXINLISHUAIJIEDEXIAOSHUFENWEISANZU。YIZUJIESHOUPDE-9ZUDUANYAOWUZHILIAO,LINGYIZUYONGPDE-5ZUZHIJIXIDINEIFEIZHILIAO,DISANZUZEFUYONGANWEIJI。

ZHILIAOSIZHOUHOU,FUYONGANWEIJIDEXIAOSHUWANQUANFAZHANCHENGXINLISHUAIJIE,ERJIESHOUPDE-5ZUZHIJIHUOPDE-9ZUZHIJIZHILIAODEXIAOSHU,QIXINZANGJIROUGONGNENGHEGUIMODOUBIAOXIANCHUXIANZHUGAISHAN,XINZANGBENGXUENENGLIHUIFUDAOJIEJINZHENGCHANG。

WEILEBIJIAOPDE-5HEPDE-9YIZHIJIDUIXINGONGNENGDEYINGXIANG,SUIHOUYANJIURENYUANYONGYIZHONGHUAXUEWUZHISIWEIYIBANDEXIAOSHU,ZHEIZHONGHUAXUEWUZHIKEGUANBIPDE-5DIAOJIEDEXINZANGBAOHUXINGXINHAOTONGLU。ZAIZHEIYIZUXIAOSHUZHONG,YONGPDE-5YIZHIJIZHILIAODEXIAOSHUMEIYOUYINGXIANG。RANER,DANGFUYONGPDE-9ZUZHIJIHOU,DONGWUXINZANGXIANSHICHUMINGXIANGAISHAN。YANJIUTUANDUIBIAOSHI,ZHEIYIFAXIANSHUOMINGLEYIGEGAINIAN:XINJISHUAIJIESHIYOULIANGGEDULIDEXINHAOJILIANFANYINGQUEXIANYINFADE,MEIYIZHONGXINHAOTONGLUDOUYOUBUTONGDEMEIDIAOJIE,BINGQIESHOUYIYUBUTONGDELIAOFA。

KassSHUO:“SHIJISHANG,ZHEIBIAOMING,JISHIYIGETONGLUHUAILE,BAOHULINGYIGETONGLUDEGONGNENGYEKEYIBIMIANJIBINGFASHENG。”

原文链接:

Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. However, cGMP stimulation alone is limited by counter-adaptions including PDE upregulation. Furthermore, although PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signalling is often depressed by heart disease. PDEs controlling natriuretic-peptide-coupled cGMP remain uncertain. Here we show that cGMP-selecive PDE9A is expressed in the mammalian heart, including humans, and is upregulated by hypertrophy and cardiac failure. PDE9A regulates natriuretic-peptide- rather than nitric-oxide-stimulated cGMP in heart myocytes and muscle, and its genetic or selective pharmacological inhibition protects against pathological responses to neurohormones, and sustained pressure-overload stress. PDE9A inhibition reverses pre-established heart disease independent of nitric oxide synthase (NOS) activity, wheras PDE5A inhibition requires active NOS. Transcription factor activation and phosphoproteome analyses of myocytes with each PDE selectively inhibited reveals substantial differential targeting, with phosphorylation changes from PDE5A inhibition being more sensitive to NOS activation. Thus, unlike PDE5A, PDE9A can regulate cGMP signalling independent of the nitric oxide pathway, and its role in stress-induced heart disease suggests potential as a therapeutic target.

期刊名:    日期:2015-03-20
DOI:10.1038/nature14332    作者:Dong I. Lee