Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway
Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway
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DOI：
10.1007/s10103-016-2099-0
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发表时间：
2016
影响因子：
2.1
通讯作者：
Xiaodong Yan;Juan-fang Liu;Zhengping Zhang;Wenhao Li;Siguo Sun;Jian Zhao;Xin Dong;Jixian Qian;Honghui Sun
中科院分区：
文献类型：
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作者：
Xiaodong Yan;Juan-fang Liu;Zhengping Zhang;Wenhao Li;Siguo Sun;Jian Zhao;Xin Dong;Jixian Qian;Honghui Sun
低强度激光（LLL）照射可促进神经元分化，但其机制尚不清楚。脑源性神经营养因子（Brain-derived neurotrophic factor，BDNF）是一种重要的神经营养因子，对神经元的分化和存活起着重要的作用。因此，本研究旨在通过钙离子成像、药理学检测、RNA干扰、免疫细胞化学、Western blot和qPCR等方法，探讨LLL照射对培养的背根神经节神经元（dorsal root ganglion neurons，DRGNs）BdnfmRNA转录的影响，以及LLL诱导BdnfmRNA转录的分子途径。我们发现LLL通过三磷酸肌醇受体（IP 3R）敏感的钙（Ca 2+）库介导的Ca 2+释放，诱导[Ca 2 +] i水平、BdnfmRNA转录、cAMP反应元件结合蛋白（CREB）磷酸化和细胞外信号调节激酶（ERK）磷酸化的增加。阻断Ca ~（2+）可增加抑制的BdnfmRNA转录、CREB磷酸化和ERK磷酸化。下调磷酸化（p）-CREB可降低LLL触发的BdnfmRNA转录。此外，使用PD 98059抑制剂阻断ERK可减少LLL诱导的p-CREB和BdnfmRNA转录。综上所述，这些发现确立了Ca 2 +-ERK-CREB级联作为一个潜在的信号通路参与LLL诱导的BdnfmRNA转录。据我们所知，这是第一个报告的Ca 2+依赖BdnfmRNA转录触发LLL的机制。这些发现可能有助于进一步探索LLL触发神经再生的复杂分子信号网络，也可能为LLL的临床应用提供实验证据。
Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation onBdnfmessenger RNA (mRNA) transcription and the molecular pathway involved in LLL-inducedBdnfmRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca2+imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca2+]ilevel,BdnfmRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca2+release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca2+) stores. Blockade of Ca2+increase suppressedBdnfmRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reducedBdnfmRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB andBdnfmRNA transcription induced by LLL. Taken together, these findings establish the Ca2+-ERK-CREB cascade as a potential signaling pathway involved in LLL-inducedBdnfmRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca2+-dependentBdnfmRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.