Pike M C, Kredich N M, Snyderman R
Proc Natl Acad Sci U S A. 1978 Aug;75(8):3928-32. doi: 10.1073/pnas.75.8.3928.
The chemotactic response of motile bacteria requires the methylation of specific proteins by S-adenosyl-L-methionine. To determine whether methylation is required for the chemotaxis of human leukocytes, we studied the effects of inhibition of S-adenosyl-L-methionine-mediated methylation on monocyte chemotactic responsiveness. Methylation was inhibited in monocytes by treating the cells with substances that produced elevations in intracellular S-adenosyl-L-homocysteine, a competitive inhibitor of S-adenosyl-L-methionine methylation. Treatment of isolated monocytes with the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, plus exogenous adenosine and L-homocysteine thiolactone increased intracellular S-adenosyl-L-homocysteine levels by as much as 1500-fold. Concomitant with increases in S-adenosyl-L-homocysteine were a decrease in monocyte protein carboxy-O-methylation as well as a marked inhibition of monocyte chemotactic responsiveness. Conditions that almost completely inhibited methylation and chemotaxis did not depress monocyte phagocytosis, indicating that this latter function either is independent of S-adenosyl-L-methionine-mediated methylation or is extremely resistant to inhibition of such reactions by S-adenosyl-L-homocysteine. These studies indicate that S-adenosyl-L-methionine-mediated methylation is required for the chemotaxis of eukaryotic cells and that the chemotactic and phagocytic functions of human monocytes have different requirements for methylation.
运动细菌的趋化反应需要特定蛋白质被S-腺苷-L-甲硫氨酸甲基化。为了确定甲基化对于人类白细胞趋化性是否必要，我们研究了抑制S-腺苷-L-甲硫氨酸介导的甲基化对单核细胞趋化反应性的影响。通过用能使细胞内S-腺苷-L-高半胱氨酸升高的物质处理细胞来抑制单核细胞中的甲基化，S-腺苷-L-高半胱氨酸是S-腺苷-L-甲硫氨酸甲基化的竞争性抑制剂。用腺苷脱氨酶抑制剂erythro-9-(2-羟基-3-壬基)腺嘌呤、外加外源性腺苷和L-高半胱氨酸硫内酯处理分离的单核细胞，可使细胞内S-腺苷-L-高半胱氨酸水平升高多达1500倍。伴随S-腺苷-L-高半胱氨酸增加的是单核细胞蛋白质羧基-O-甲基化减少以及单核细胞趋化反应性受到显著抑制。几乎完全抑制甲基化和趋化作用的条件并未降低单核细胞的吞噬作用，这表明后一种功能要么独立于S-腺苷-L-甲硫氨酸介导的甲基化，要么对S-腺苷-L-高半胱氨酸抑制此类反应具有极强的抗性。这些研究表明，S-腺苷-L-甲硫氨酸介导的甲基化是真核细胞趋化性所必需的，并且人类单核细胞的趋化和吞噬功能对甲基化有不同的需求。
