THE ROLE OF BLOOD-PLATELETS IN NUCLEOSIDE METABOLISM - REGULATION OF PLATELET THYMIDINE PHOSPHORYLASE
THE ROLE OF BLOOD-PLATELETS IN NUCLEOSIDE METABOLISM - REGULATION OF PLATELET THYMIDINE PHOSPHORYLASE
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DOI：
10.1016/0027-5107(88)90075-9
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发表时间：
1988-07-01
期刊：
影响因子：
--
通讯作者：
MACPHEE, DG
中科院分区：
文献类型：
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作者：
SHAW, T;SMILLIE, RH;MACPHEE, DG
血小板是哺乳动物血液中最小的细胞成分。由于血小板体积小，其表面积体积比异常大，对多种生理和环境刺激非常敏感。血小板缺乏细胞核，但大多数具有功能性线粒体，并且能够进行厌氧和有氧能量代谢，为此它们利用各种底物，包括许多对其他（有核）细胞具有细胞毒性和基因毒性的底物。核酸前体是潜在的基因毒性化合物之一，血小板对这些化合物显然有着无法满足的胃口。特别是血小板积极清除腺嘌呤和腺苷，它们将其转化为核苷酸并用于能量代谢，但它们也迅速磷酸化胸腺嘧啶并将胸腺嘧啶释放到细胞外培养基中。此外，血小板含有不可代谢的腺嘌呤核苷酸膜结合池，它们在强激动剂作用下分泌腺嘌呤核苷酸。综上所述，这些观察结果表明血小板在核酸前体代谢中起重要作用。在以前的论文中，我们已经表明，大多数胸苷磷酸化酶活性存在于正常人血液中的血小板细胞质中。在这里，我们证明了这种酶的活性可以以剂量依赖性的方式调节，不仅被认为是血小板激动剂和拮抗剂的物质，而且还被一些被认为是有毒的，诱变的和/或致癌的化合物。我们提出的数据为我们之前的建议提供了额外的支持，即血小板调节胸腺嘧啶稳态，并进一步暗示这是正常的，生理的，血小板功能。初步结果表明，血小板胸苷代谢测定可提供广泛应用的数据。
Blood platelets are the smallest cellular elements in mammalian blood. Because of their small size, platelets have an unusually large surface area: volume ratio and are exquisitely sensitive to a multitude of physiological and environmental stimuli. Platelets lack nuclei, but most possess functional mitochondria and remain capable of both anaerobic and aerobic energy metabolism, for which they utilise a variety of substrates including many which are cytotoxic and genotoxic for other (nucleated) cells. Nucleic acid precursors are amongst the potentially genotoxic compounds for which platelets have an apparently insatiable appetite. In particular platelets actively scavenge adenine and adenosine, which they convert to nucleotides and use in energy metabolism, but they also rapidly phosphorylyse thymidine and liberate thymine into the extracellular medium. In addition, platelets contain non-metabolisable membrane-bound pools of adenine nucleotides which they secrete in response to strong agonists. Taken together, these observations suggest that blood platelets play an important role in nucleic acid precursor metabolism. In the previous paper we have shown that most thymidine phosphorylase activity present in normal human blood resides in the cytoplasm of platelets. Here we demonstrate that this enzyme activity can be modulated in a dose-dependent fasion, not only by substances recognised as platelet agonists and antagonists, but also by some compounds which are considered to be toxic, mutagenic and/or carcinogenic. The data which we present provide additional support for our previous suggestion that platelets regulate thymidine homeostasis and further imply that this is the normal, physiological, platelet function. Preliminary results suggest that assays of blood platelet thymidine metabolism may provide data with a wide variety of applications.