Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.
Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.
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丙酮酸脱氢酶缺乏症中蛋白质和 mRNA 的异质表达。
DOI：
10.1073/pnas.85.19.7336
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发表时间：
1988
影响因子：
11.1
通讯作者：
Pons,G
中科院分区：
文献类型：
--
作者：
Wexler,ID;Kerr,DS;Ho,L;Lusk,MM;Pepin,RA;Javed,AA;Mole,JE;Jesse,BW;Thekkumkara,TJ;Pons,G
丙酮酸脱氢酶复合物的第一组分丙酮酸脱氢酶[丙酮酸：脂酰胺2-氧化还原酶（脱羧和受体乙酰化），EC 1.2.4.1]缺乏与乳酸酸中毒和中枢神经系统功能障碍有关。使用丙酮酸脱氢酶特异性抗体和编码其两个α和β亚基的cdna，我们鉴定了11例患者的丙酮酸脱氢酶缺乏症。免疫和RNA印迹分析发现三种不同的模式。(i) 7例患者有免疫检测到的丙酮酸脱氢酶α和β蛋白交叉反应物质。（ii）两名患者的α或β亚基均未检测到交叉反应蛋白，但α和β亚基的mRNA含量正常。（iii）其余两例患者也未检测到交叉反应蛋白，但仅丙酮酸脱氢酶α亚基mRNA量减少。这些结果表明丙酮酸脱氢酶活性的丧失可能与缺乏或催化活性不高的蛋白质有关，并且在这种酶缺乏的情况下，其中一个亚基的mRNA也可能缺失。当其中一个亚基的mRNA缺失时，两个蛋白质亚基都缺失，这表明影响其中一个亚基蛋白表达的突变会导致剩余的未复合亚基不稳定。结果表明，几种不同的突变导致了丙酮酸脱氢酶缺乏症的分子异质性。
Deficiency of pyruvate dehydrogenase [pyruvate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1], the first component of the pyruvate dehydrogenase complex, is associated with lactic acidosis and central nervous system dysfunction. Using both specific antibodies to pyruvate dehydrogenase and cDNAs coding for its two alpha and beta subunits, we characterized pyruvate dehydrogenase deficiency in 11 patients. Three different patterns were found on immunologic and RNA blot analyses. (i) Seven patients had immunologically detectable crossreactive material for the alpha and beta proteins of pyruvate dehydrogenase. (ii) Two patients had no detectable crossreactive protein for either the alpha or beta subunit but had normal amounts of mRNA for both alpha and beta subunits. (iii) The remaining two patients also had no detectable crossreactive protein but had diminished amounts of mRNA for the alpha subunit of pyruvate dehydrogenase only. These results indicate that loss of pyruvate dehydrogenase activity may be associated with either absent or catalytically inactive proteins, and in those cases in which this enzyme is absent, mRNA for one of the subunits may also be missing. When mRNA for one of the subunits is lacking, both protein subunits are absent, suggesting that a mutation affecting the expression of one of the subunit proteins causes the remaining uncomplexed subunit to be unstable. The results show that several different mutations account for the molecular heterogeneity of pyruvate dehydrogenase deficiency.