4-Hydroxynonenal, a product of cellular lipid peroxidation, which modulates c-myc and globin gene expression in K562 erythroleukemic cells.
4-Hydroxynonenal, a product of cellular lipid peroxidation, which modulates c-myc and globin gene expression in K562 erythroleukemic cells.
复制标题
4-Hydroxynonenal，细胞脂质过氧化的产物，可调节 K562 红白血病细胞中的 c-myc 和球蛋白基因表达。
作者：
Vito Michele Fazio;G. Barrera;Stefano Martinotti;M. Farace;Barbara Giglioni;Luigi Frati;V. Manzari;M. U. Dianzani
一些研究指出，细胞脂质过氧化与细胞增殖和肿瘤转化之间存在负相关。在这里，我们发现，接近正常细胞水平的4-羟基壬烯醛(HNE)(在1到3微米的范围内)可以特异性地诱导K562细胞c-myc和γ-珠蛋白mRNA的表达变化，而不会产生任何毒性效应或影响细胞活力。由于我们已经确定K562细胞具有无法检测到的内源性脂质过氧化水平，所有这些效应都可以归因于外源性HNE处理。1微米HNE作用1h后，c-myc基因表达水平在前4h短暂下降，随后反弹至较高水平，4d后恢复到基础水平。连续实验表明，在HNE处理后20分钟，转录阻断和随后的转录后调节。根据S1定位，c-myc转录本在两个主要组成起始位点(P1和P2)上发生了mRNA变化。伽玛珠蛋白基因表达水平同时增加3-4倍，但没有观察到管家基因表达的显著变化。根据这些结果，似乎在人红白血病K562细胞中恢复到接近正常细胞水平的HNE浓度可以调节特定基因的表达。
Several studies point to the existence of an inverse correlation between cellular lipid peroxidation and both cell proliferation and neoplastic transformation. Here, we show that 4-hydroxynonenal (HNE) concentrations close to the level found in normal cells (in the range of 1 and 3 microM) can specifically induce changes in the expression of c-myc and gamma-globin mRNA in K562 cells, without inducing any toxic effects or affecting cell viability. Since we have determined that K562 cells have undetectable levels of endogenous lipid peroxidation, all these effects can be assigned to the exogenous HNE treatment. After a 1-h treatment with 1 microM HNE, c-myc mRNA levels decrease transiently during the first 4 h, rebounding later to higher levels, and normalizing to basal expression after 4 days. Run-on experiments show a transient transcriptional block 20 min after HNE treatment and subsequent posttranscriptional regulation. According to S1 mapping, mRNA changes are exerted on c-myc transcripts initiated from both the principal constitutive start sites (P1 and P2). gamma-Globin mRNA levels concomitantly increase 3- to 4-fold, but no significant changes of housekeeping gene expression are observed. On the basis of these results it appears that the restoration in human erythroleukemic K562 cells of HNE concentrations closer to the level in normal cells can modulate the expression of specific genes.
转录和转录后机制对小鼠红白血病细胞 c-myc 表达调节的贡献。
影响因子：
10.5
作者：
Nepveu,A;Marcu,KB;Skoultchi,AI;Lachman,HM
通讯作者：
Lachman,HM
白血病细胞分化过程中腺苷酸环化酶活性升高。
影响因子：
3.7
作者：
Fontana,J;Miksis,G;Durham,J
通讯作者：
Durham,J