Enzymatic methyl esterification of erythrocyte membrane proteins is impaired in chronic renal failure. Evidence for high levels of the natural inhibitor S-adenosylhomocysteine.

Enzymatic methyl esterification of erythrocyte membrane proteins is impaired in chronic renal failure. Evidence for high levels of the natural inhibitor S-adenosylhomocysteine.
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红细胞膜蛋白的酶促甲基酯化在慢性肾衰竭中受损。

DOI:
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发表时间:
1993
影响因子:
15.9
通讯作者:
N. D. De Santo
N. D. De Santo
中科院分区:
医学1区
文献类型:
--
作者:
A. Perna;D. Ingrosso;V. Zappia;P. Galletti;G. Capasso;N. D. De Santo

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酶蛋白羧甲基转移酶II型最近被证明在受损蛋白的修复中起着至关重要的作用。s -腺苷蛋氨酸(AdoMet)是该反应的甲基供体,其去甲基化产物s -腺苷同型半胱氨酸(AdoHcy)是该反应以及大多数AdoMet依赖性甲基化的天然抑制剂。我们检查了慢性肾衰竭(CRF)患者保守治疗或血液透析的红细胞膜蛋白甲基化,以检测甲基化模式可能的改变,在红细胞功能受损的情况下。与对照组相比,我们观察到两组的膜蛋白甲基酯化显著减少。细胞骨架成分锚蛋白的减少尤其明显,锚蛋白被认为与膜的稳定性和完整性有关。此外,我们观察到AdoHcy水平上升了几倍,而AdoMet浓度与对照组相当,导致[AdoMet]/[AdoHcy]比率较低(P < 0.001)。我们的研究结果表明,这种蛋白质翻译后修饰的损伤与CRF中高adhcy细胞内浓度有关。这些数据与CRF中结构损伤在红细胞膜蛋白中积累并没有得到充分修复的观点一致。
The enzyme protein carboxyl methyltransferase type II has been recently shown to play a crucial role in the repair of damaged proteins. S-adenosylmethionine (AdoMet) is the methyl donor of the reaction, and its demethylated product, S-adenosylhomocysteine (AdoHcy), is the natural inhibitor of this reaction, as well as of most AdoMet-dependent methylations. We examined erythrocyte membrane protein methyl esterification in chronic renal failure (CRF) patients on conservative treatment or hemodialyzed to detect possible alterations of the methylation pattern, in a condition where a state of disrupted red blood cell function is present. We observed a significant reduction in membrane protein methyl esterification in both groups, compared to control. The decrease was particularly evident for cytoskeletal component ankyrin, which is known to be involved in membrane stability and integrity. Moreover, we observed a severalfold rise in AdoHcy levels, while AdoMet concentration was comparable to that detected in the control, resulting in a lower [AdoMet]/[AdoHcy] ratio (P < 0.001). Our findings show an impairment of this posttranslational modification of proteins, associated with high AdoHcy intracellular concentration in CRF. The data are consistent with the notion that, in CRF, structural damages accumulate in erythrocyte membrane proteins, and are not adequately repaired.
DOI: 10.1172/jci112157
发表时间: 1985
期刊: The Journal of clinical investigation
影响因子: --
作者:
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DOI: --
发表时间: 1984
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DOI: --
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期刊: The Journal of biological chemistry
影响因子: --
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DOI: 10.1038/ki.1989.216
发表时间: 1989
影响因子: 19.6
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发表时间: 1989
影响因子: 19.6
作者:
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