Calderon T M, Schneiderman N, Michl J, Christman J K
Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10021.
Cell Differ Dev. 1989 May;26(3):181-90. doi: 10.1016/0922-3371(89)90749-1.
5,5'-Dimethyloxazolidine-2,4-dione (DMO), a weak non-metabolizable acid, is commonly utilized for determining intracellular pH. In these studies, DMO was tested as an inducer of differentiation on the basis that its uptake and subsequent dissociation might transiently raise intracellular pH and activate ion-fluxes critical for triggering maturation. After 5 days of exposure to 40 mM DMO, greater than 60% of HL-60 cells displayed phenotypic and functional changes characteristic of mature granulocytes. As with other inducers of HL-60 cell differentiation, commitment to differentiation required culture in the presence of DMO for more than 24 h, indicating that if transient effects on pH or ion-fluxes occurred, they were not sufficient to trigger this process. DMO was either weak or inactive as an inducer of murine erythroleukemia cell (FLC) differentiation. Although other weak acids and bases triggered differentiation of both HL-60 cells and FLC, the spectrum of response differed markedly between the two lines. These results suggest that: (1) a number of common buffering agents have the potential to alter cell phenotype, and (2) their effects must be evaluated for each individual cell type.
5,5'-二甲基恶唑烷-2,4-二酮(DMO)是一种弱的不可代谢酸,常用于测定细胞内pH值。在这些研究中,DMO作为分化诱导剂进行了测试,基于其摄取和随后的解离可能会短暂升高细胞内pH值并激活触发成熟所需的离子通量。在暴露于40 mM DMO 5天后,超过60%的HL-60细胞表现出成熟粒细胞特有的表型和功能变化。与HL-60细胞分化的其他诱导剂一样,向分化的定向需要在DMO存在下培养超过24小时,这表明如果对pH值或离子通量有短暂影响,它们不足以触发这个过程。DMO作为小鼠红白血病细胞(FLC)分化的诱导剂要么作用微弱要么无活性。尽管其他弱酸和弱碱可触发HL-60细胞和FLC的分化,但两系之间的反应谱明显不同。这些结果表明:(1)许多常见的缓冲剂有改变细胞表型的潜力,(2)必须针对每种细胞类型评估它们的作用。