Systematic expression profiling of the gastric H+/K+ ATPase in human tissue

Systematic expression profiling of the gastric H+/K+ ATPase in human tissue
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人体组织中胃 H /K ATP 酶的系统表达谱

DOI:
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发表时间:
2007
影响因子:
1.9
通讯作者:
T. Klein
T. Klein
中科院分区:
医学4区
文献类型:
--
作者:
M. Herrmann;Jens Selige;S. Raffael;G. Sachs;A. Brambilla;T. Klein

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Objective.钾竞争性酸阻断剂(P-CAB)是一组新型的胃H+/K+ ATP酶竞争性可逆抑制剂。我们的目的是通过检查人体广泛组织中胃H+/K + ATP酶的表达谱来确定H+/K + ATP酶的表达位点,这些位点是这些化合物的潜在靶点。材料和方法。通过定量mRNA分析(TaqMan PCR)进行表达谱分析。通过Western印迹和免疫组织化学(IHC)进一步研究α亚基mRNA阳性的组织中胃H+/K+ ATP酶蛋白的存在。结果除了胃中非常高的表达水平外,肾上腺、小脑和胰腺对胃H+/K+ ATP酶的α亚基给出了出乎意料的阳性mRNA信号。然而,它们对β亚基的mRNA呈阴性,Western blot和IHC对α和β亚基蛋白呈阴性。另一组具有低α亚基mRNA表达的组织,包括额叶皮质、皮质灰质、睾丸、胸腺和喉粘膜下层,也发现α和β亚基蛋白均为阴性。与小鼠肾脏相比,人肾脏中未检测到胃H+/K+ ATP酶。结论.因此,我们得出结论,在人类中表达显著水平的P-CAB靶胃H+/K+ ATP酶的唯一器官是胃。
Objective. The potassium-competitive acid blockers (P-CABs), comprise a new, innovative group of competitive and reversible inhibitors of the gastric H+/K+ ATPase. Our aim was to identify sites of expression of the H+/K+ ATPase that are potential targets of these compounds by examining the expression profile of the gastric H+/K+ ATPase in the human body from a broad range of tissues. Material and methods. Expression profiling was done by quantitative mRNA analysis (TaqMan PCR). Tissues that were mRNA-positive for the alpha subunit were investigated further by Western blot and immunohistochemistry (IHC) for the presence of gastric H+/K+ ATPase protein. Results. In addition to the very high expression levels in the stomach, the adrenal gland, cerebellum and pancreas gave unexpectedly positive mRNA signals for the alpha subunit of gastric H+/K+ ATPase. However, they were negative for mRNA of the beta subunit, and Western blot and IHC were negative for alpha and beta subunit protein. Another group of tissues with low alpha subunit mRNA expression including the frontal cortex, cortex grey matter, testis, thymus and larynx submucosa were also found negative for both alpha and beta subunit protein. In contrast to mouse kidney, no gastric H+/K+ ATPase could be detected in human kidney. Conclusions. We therefore conclude that the only organ in humans expressing significant levels of the P-CAB target gastric H+/K+ ATPase is the stomach.
DOI: 10.1053/bega.2002.0338
发表时间: 2002
期刊: Best practice & research. Clinical gastroenterology
影响因子: --
作者:
Sachs,George;Shin,JaiMoo;Vagin,Olga;Munson,Keith;Weeks,David;Scott,DavidR;Voland,Petra
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DOI: --
发表时间: 1988
影响因子: 4.4
作者:
Fain,GL;Smolka,A;Cilluffo,MC;Fain,MJ;Lee,DA;Brecha,NC;Sachs,G
通讯作者: Sachs,G
DOI: --
发表时间: 1990
期刊: The Journal of biological chemistry
影响因子: --
作者:
Canfield,VA;Okamoto,CT;Chow,D;Dorfman,J;Gros,P;Forte,JG;Levenson,R
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DOI: 10.1152/ajprenal.1995.268.3.f363
发表时间: 1995
期刊: The American journal of physiology
影响因子: --
作者:
Callaghan,JM;Tan,SS;Khan,MA;Curran,KA;Campbell,WG;Smolka,AJ;Toh,BH;Gleeson,PA;Wingo,CS;Cain,BD
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胃H,K-ATP酶K竞争性抑制剂位点的突变分析。
DOI: 10.1021/bi0105328
发表时间: 2001
期刊: Biochemistry
影响因子: 2.9
作者:
Vagin,O;Munson,K;Lambrecht,N;Karlish,SJ;Sachs,G
通讯作者: Sachs,G