Gene expression profiling of hypoxia signaling in human hepatocellular carcinoma cells.
Gene expression profiling of hypoxia signaling in human hepatocellular carcinoma cells.
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DOI：
10.1152/physiolgenomics.00045.2004
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发表时间：
2005-08
影响因子：
4.6
通讯作者：
A. Vengellur;J. Phillips;J. Hogenesch;J. LaPres
中科院分区：
文献类型：
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作者：
A. Vengellur;J. Phillips;J. Hogenesch;J. LaPres
细胞、局部和有机体对低O2可用性的反应发生在无氧代谢和伤口愈合等过程以及中风和癌症等病理条件下。这些反应包括糖酵解活性、血管形成、呼吸和红细胞生成的增加。这些反应部分由低氧诱导因子（HIF）介导，HIF从一组铁和O2依赖性羟化酶接收O2水平的信息。低氧模拟物，如氯化钴、氯化镍和去铁胺，通过改变这些羟化酶的铁状态来模拟低氧。为了确定这些模拟物是否是自然诱发的较低O2张力的适当替代品，我们使用高密度寡核苷酸阵列比较了Hep3B细胞系的转录反应。一组核心基因被鉴定为所有四种治疗（缺氧、钴、镍和去铁胺）所共有，包括糖酵解酶、细胞周期调节因子和凋亡基因。重要的是，钴、镍和去铁胺影响了不受细胞缺氧影响的不同基因组的转录。这些全球缺氧反应表明适应和程序性细胞死亡之间的平衡行为，并建议谨慎使用低氧模拟物作为体内发生的低O2张力的替代品。
Cellular, local, and organismal responses to low O2 availability occur during processes such as anaerobic metabolism and wound healing and pathological conditions such as stroke and cancer. These responses include increases in glycolytic activity, vascularization, breathing, and red blood cell production. These responses are mediated in part by the hypoxia-inducible factors (HIFs), which receive information on O2 levels from a group of iron- and O2-dependent hydroxylases. Hypoxia mimics, such as cobalt chloride, nickel chloride, and deferoxamine, act to simulate hypoxia by altering the iron status of these hydroxylases. To determine whether these mimics are appropriate substitutes for the lower O2 tension evoked naturally, we compared transcriptional responses of a Hep3B cell line using high-density oligonucleotide arrays. A battery of core genes was identified that was shared by all four treatments (hypoxia, cobalt, nickel, and deferoxamine) including glycolytic enzymes, cell cycle regulators, and apoptotic genes. Importantly, cobalt, nickel, and deferoxamine influenced transcription of distinct sets of genes that were not affected by cellular hypoxia. These global responses to hypoxia indicate a balancing act between adaptation and programmed cell death and suggest caution in the use of hypoxia mimics as substitutes for the low O2 tension that occurs in vivo.