Cycling exercise affects the expression of apoptosis-associated microRNAs after spinal cord injury in rats.

Cycling exercise affects the expression of apoptosis-associated microRNAs after spinal cord injury in rats.
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DOI:
10.1016/j.expneurol.2010.08.032
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发表时间:
2010-11
影响因子:
5.3
通讯作者:
Houle, John D.
Houle, John D.
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Gang;Keeler, Benjamin E.;Zhukareva, Victoria;Houle, John D.

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脊髓损伤 (SCI) 有两个主要方面:急性原发性机械损伤和由炎症、兴奋性毒性、细胞凋亡和脱髓鞘引起的继发性组织损伤的进行性阶段。 MicroRNA (miR) 是约 22 个核苷酸的小型非蛋白质编码 RNA,在转录后水平发挥作用以调节基因表达。它们在细胞增殖和程序性细胞死亡等稳态过程中发挥重要作用。在受伤的大鼠脊髓中,我们对 miR 及其参与细胞凋亡途径的下游靶标进行了表达分析,并使用损伤后循环运动来测试 miR 表达的活动依赖性可塑性。我们发现,SCI 会导致 miR Let-7a 和 miR16 的表达增加,而运动会导致 miR21 水平升高和 miR15b 水平降低。 miR 表达的这些变化与其靶基因的表达变化相关:促凋亡(PTEN、PDCD4 和 RAS mRNA 减少)和抗凋亡(Bcl-2 mRNA 增加)靶基因。这伴随着 caspase-7 和 caspase-9 mRNA 的下调以及 caspase-7 蛋白水平的降低。这些结果表明,运动可能通过作用于多个 miR 及其靶标而产生有益效果,这些靶标有助于 SCI 后细胞凋亡的功能调节。
There are two major aspects to a spinal cord injury (SCI): an acute, primary mechanical trauma and a progressive phase of secondary tissue damage provoked by inflammation, excitotoxicity, apoptosis and demyelination. MicroRNAs (miRs) are small, ~22 nucleotide, non-protein-coding RNAs that function at the post-transcriptional level to regulate gene expression. They have important roles in homeostatic processes such as cell proliferation and programmed cell death. In the injured rat spinal cord we performed an expression analysis of miRs and their downstream targets involved in apoptotic pathways and used post-injury cycling exercise to test for activity dependent plasticity of miR expression. We show that SCI results in increased expression of miR Let-7a and miR16 while exercise leads to elevated levels of miR21 and decreased levels of miR15b. These changes in miR expression are correlated with changes in expression of their target genes: pro-apoptotic (decreased PTEN, PDCD4 and RAS mRNA) and anti-apoptotic (increased Bcl-2 mRNA) target genes. This is accompanied by a down regulation of mRNA for caspase-7 and caspase-9 and reduced levels of caspase-7 protein. These results indicates possible beneficial effects of exercise through action on multiple miRs and their targets that contribute to the functional regulation of apoptosis after SCI.
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