Na,K-ATPase inhibitors from bovine hypothalamus and human plasma are different from ouabain: nanogram scale CD structural analysis.
Na,K-ATPase inhibitors from bovine hypothalamus and human plasma are different from ouabain: nanogram scale CD structural analysis.
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来自牛下丘脑和人血浆的 Na,K-ATP 酶抑制剂与哇巴因不同：纳克级 CD 结构分析。
DOI：
10.1021/bi00031a010
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
HaupertJr,GT
中科院分区：
文献类型：
--
作者：
Zhao,N;Lo,LC;Berova,N;Nakanishi,K;Tymiak,AA;Ludens,JH;HaupertJr,GT
摘要：哺乳动物钠和钾转运腺苷三磷酸酶（Na，K-ATP酶或钠泵），一种在哺乳动物组织中具有重要生理意义的质膜酶，与植物来源的洋地黄糖苷特异性高亲和力结合，提出了可能存在洋地黄的哺乳动物类似物的可能性。我们先前从牛下丘脑中分离并结构表征了植物糖苷哇巴因的新型异构体，其结构上的不同仅在于类固醇部分的连接位点和/或立体化学[Tymiak et al.等人（1993）Proc. Acad. Sci. USA 90，8189-8193]，Hamlyn和同事报道了从人血浆中纯化的分子，其通过质谱法不能与植物哇巴因区分开[Hamlyn et al.等人（1991）Proc. Acad. Sci. USA 88，6259-6263]。由于鼠李糖苷强心甾体不是已知的哺乳动物来源的天然产物，因此比较这两种纯分离物以确定是否发现相同或结构不同的化合物变得重要。我们的结果表明，人和牛的Na，K-ATP酶抑制剂是相同的，但不同于植物哇巴因。这支持了人钠泵可能受哺乳动物洋地黄苷类似物的特殊生理调节的观点。实验证据表明，内源性洋地黄样Na，K-ATP酶抑制剂通过调节肾钠排泄与体液和电解质稳态有关，在失调状态下，与流行的人类疾病高血压的发病机制有关，刺激了分离和表征这种化合物的努力（Haber和Haupert，1987;后藤等人，1992年）。使用亲和层析结合HPLC，我们纯化了牛下丘脑Na，K-ATP酶抑制因子HIF 1（Tymiak，1993）。它的分子量为584，与哇巴因同重。然后发现HIF是an-L鼠李糖苷，
Revised Manuscript Received May 18, 1995® abstract: The specific, high affinity binding of plant-derived digitalis glycosides by the mammalian sodium and potassium transporting adenosine triphosphatase (Na, K-ATPase, or sodium pump), a plasma membrane enzyme with critical physiologicalimportance in mammalian tissues, has raised the possibility that a mammalian analog of digitalis might exist. We previously isolated and structurally characterized from bovine hypothalamus a novel isomer of the plant glycoside, ouabain, which differs structurally only in the attachment site and/or the stereochemistry of the steroid moiety [Tymiak et al.(1993) Proc. Natl. Acad. Sci. USA 90, 8189-8193], Hamlyn and co-workers reported a molecule purified from human plasma which by mass spectrometry could not be distinguished from plant ouabain [Hamlyn et al.(1991) Proc. Natl. Acad. Sci. USA 88, 6259—6263]. Since rhamnoside cardiotonic steroids are not known as natural products from mammalian sources, it became important to compare these two pure isolates to determine if the same or structurally distinct compoundshad been found. Our results indicate that the human and bovine Na, K-ATPase-inhibitors are identical, but different from plant ouabain. This supports the notion thatthe human sodium pump may be under specificphysiological regulation by a mammalian analog of the digitalis glycosides.Experimental evidence linking an endogenous digitalislike Na, K-ATPase inhibitor to fluid and electrolyte homeo-stasis through regulation of renal sodium excretion and, in the case of dysregulated states, to the pathogenesis of a prevalent human disease, hypertension, stimulated efforts to isolate and characterize such a compound (Haber and Haupert, 1987; Goto et al., 1992). Using affinity chromatography combined with HPLC we purified a bovine hypothalamic Na, K-ATPase inhibitor factor, HIF1 (Tymiak, 1993). It has a molecular weight of 584, making it isobaric with ouabain. HIF was then found to be an-L rhamnoside,