Lever J E
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
Environ Health Perspect. 1989 Mar;80:173-80. doi: 10.1289/ehp.8980173.
The long-term renal epithelial cell line LLC-PK1 expresses at confluence several differentiated characteristics of renal proximal tubule including Na/glucose cotransport and several brush border membrane hydrolases. The differentiation-inducing chemical hexamethylene bisacetamide (HMBA) triggers a dramatic induction of Na+/glucose symport, trehalase and maltase, expressed as an increase in the number of cells in the culture that express the differentiated phenotype. Characteristics of the induction response are reviewed in terms of proposed mechanisms of inducer action. New evidence suggests that in addition to elevation of intracellular Na levels mediated by partial inhibition of the sodium pump, HMBA treatment also alters polyamine levels via effects on ornithine decarboxylase. These responses may be mediated by HMBA effects on protein kinase C activity. The possible role of polyamine fluctuations and DNA demethylation in mediating HMBA effects on differentiated gene expression is currently being investigated.
长期培养的肾上皮细胞系LLC-PK1在汇合时表现出肾近端小管的几种分化特征，包括钠/葡萄糖共转运和几种刷状缘膜水解酶。诱导分化的化学物质六甲撑双乙酰胺（HMBA）引发钠/葡萄糖协同转运、海藻糖酶和麦芽糖酶的显著诱导，表现为培养物中表达分化表型的细胞数量增加。根据诱导剂作用的提出机制对诱导反应的特征进行了综述。新证据表明，除了通过部分抑制钠泵介导细胞内钠水平升高外，HMBA处理还通过对鸟氨酸脱羧酶的作用改变多胺水平。这些反应可能由HMBA对蛋白激酶C活性的影响介导。目前正在研究多胺波动和DNA去甲基化在介导HMBA对分化基因表达影响中的可能作用。
