Transcriptional analysis of normal human fibroblast responses to microgravity stress.
Transcriptional analysis of normal human fibroblast responses to microgravity stress.
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DOI：
10.1016/s1672-0229(08)60018-2
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发表时间：
2008-03
影响因子：
9.5
通讯作者：
Wang, Eugenia
中科院分区：
文献类型：
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作者：
Liu, Yongqing;Wang, Eugenia
为了了解航天飞行如何影响细胞信号传导途径的分子机制，在STS-93航天飞机使命上飞行静止的正常人WI-38成纤维细胞。随后，从空间飞行和地面对照细胞的RNA样品被用来构建两个cDNA文库，然后进行抑制性消减杂交（SSH），以确定空间飞行特异性基因表达。SSH数据显示，与氧化应激、DNA修复和脂肪酸氧化相关的关键基因被太空飞行激活，表明细胞氧化应激的诱导。神经调节蛋白1和钙结合蛋白钙调蛋白2的上调进一步证实了这一点。另一个明显的应激信号是，太空飞行引起Ras/丝裂原活化蛋白激酶和磷脂酰肌醇-3激酶信号通路，沿着上调几个G1期细胞周期穿越基因。显示表达上调的其他基因涉及蛋白质合成和促凋亡以及促存活。功能相关基因的相互作用组分析表明，c-Myc是那些显示显着变化的基因的“枢纽”。因此，我们的研究结果表明，微重力旅行可能会影响主要与细胞应激信号相关的基因表达的变化，指导细胞凋亡或过早衰老。
To understand the molecular mechanism(s) of how spaceflight affects cellular signaling pathways, quiescent normal human WI-38 fibroblasts were flown on the STS-93 space shuttle mission. Subsequently, RNA samples from the space-flown and ground-control cells were used to construct two cDNA libraries, which were then processed for suppression subtractive hybridization (SSH) to identify spaceflight-specific gene expression. The SSH data show that key genes related to oxidative stress, DNA repair, and fatty acid oxidation are activated by spaceflight, suggesting the induction of cellular oxidative stress. This is further substantiated by the up-regulation of neuregulin 1 and the calcium-binding protein calmodulin 2. Another obvious stress sign is that spaceflight evokes the Ras/mitogen-activated protein kinase and phosphatidylinositol-3 kinase signaling pathways, along with up-regulating several G1-phase cell cycle traverse genes. Other genes showing up-regulation of expression are involved in protein synthesis and pro-apoptosis, as well as pro-survival. Interactome analysis of functionally related genes shows that c-Myc is the “hub” for those genes showing significant changes. Hence, our results suggest that microgravity travel may impact changes in gene expression mostly associated with cellular stress signaling, directing cells to either apoptotic death or premature senescence.