Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center, Temple, TX, USA.
Mol Cell Biochem. 2014 Feb;387(1-2):135-41. doi: 10.1007/s11010-013-1878-1. Epub 2013 Nov 1.
Angiotensin II(Ang II)-stimulated cardiomyocytes hypertrophy and apoptosis are associated with nuclear factor-κB (NF-κB) activation. NF-κB, a redox-sensitive transcription factor, contributes a critical role in cell death, but, Ang II-stimulated NF-κB-mediated cardiomyocytes apoptosis remains less understood. Recently, microRNAs (miRNAs) have been shown to be critical regulators in various cardiac remodeling processes; however, NF-κB-mediated miRNA's role in cardiomyocytes apoptosis remains undetermined. The miR-30b has been implicated in diverse cardiac remodeling; but, NF-κB-mediated miR-30b modulation in Ang II-induced cardiomyocytes death is currently unknown. In the present study, neonatal cardiomyocytes were pretreated with SN50, a selective cell permeable peptide inhibitor of NF-κB, or transfected with miR-30b mimetic and inhibitors separately, and then challenged with Ang II. The target gene, Bcl-2, and NF-κB transcriptional activity were analyzed. Our results demonstrated that NF-κB positively regulated miR-30b expression in Ang II-induced cardiomyocytes apoptosis, and Bcl-2 was a direct target for miR-30b. NF-κB further regulated the expression of Bcl-2 in the above setting. Furthermore, Ang II-induced cardiomyocytes apoptosis rescued by inhibiting either NF-κB or miR-30b provided an important role in cardiomyocytes cell death. We evaluated a critical role of NF-κB-mediated miR-30b modulation in Ang II-stimulated cardiomyocytes targeting Bcl-2. Our data may provide a new insight of miR-30b's role in myocardial infarction or ischemia.
血管紧张素 II（Ang II）刺激的心肌细胞肥大和凋亡与核因子-κB（NF-κB）的激活有关。NF-κB 是一种氧化还原敏感的转录因子，在细胞死亡中起着关键作用，但 Ang II 刺激的 NF-κB 介导的心肌细胞凋亡的机制仍知之甚少。最近，microRNAs（miRNAs）已被证明在各种心脏重构过程中是至关重要的调节剂；然而，NF-κB 介导的 miRNA 在心肌细胞凋亡中的作用仍未确定。miR-30b 已被牵涉到多种心脏重构中；但是，NF-κB 介导的 miR-30b 在 Ang II 诱导的心肌细胞死亡中的调控作用目前尚不清楚。在本研究中，用 NF-κB 的选择性细胞通透肽抑制剂 SN50 预处理新生心肌细胞，或分别转染 miR-30b 模拟物和抑制剂，然后用 Ang II 处理。分析了靶基因 Bcl-2 和 NF-κB 的转录活性。结果表明，NF-κB 正向调节 Ang II 诱导的心肌细胞凋亡中 miR-30b 的表达，Bcl-2 是 miR-30b 的直接靶基因。在上述情况下，NF-κB 进一步调节 Bcl-2 的表达。此外，抑制 NF-κB 或 miR-30b 均可挽救 Ang II 诱导的心肌细胞凋亡，这表明在心肌细胞死亡中发挥了重要作用。我们评估了 NF-κB 介导的 miR-30b 调节在 Ang II 刺激的心肌细胞靶向 Bcl-2 中的关键作用。我们的数据可能为 miR-30b 在心肌梗死或缺血中的作用提供了新的见解。
