The Third Affiliated Hospital of Wenzhou Medical University Department of Cardiology, Wenzhou, 325200, People's Republic of China.
The Third Affiliated Hospital of Wenzhou Medical University Department of ICU, Wenzhou, 325200, People's Republic of China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2226-2233. doi: 10.1016/j.bbrc.2018.06.142. Epub 2018 Jun 28.
The adult mammalian heart doesn't regenerate after cardiomyocyte injury, which was mainly caused by the severe and persistent effects of cardiomyopathy. Recently, some studies reported that the mammalian heart can regenerate under low oxygen environment. However, the mechanism that the mammalian heart can regenerate remains unknown. Here, we used cardiac stem cells (CSCs) to be planted in serum-free medium under hypoxia environment to understand the mechanism of HIF1α/NDUFA4L2 in the regulation of hypoxia-alleviated apoptosis. Our results revealed that hypoxia can alleviated CSCs apoptosis. Hypoxia inhibited the level of cleaved-caspase3 and stimulated the expression of stabilized HIF-1α. DMOG promotes the survival of CSCs and the protein expression of NDUFA4L2. 2-ME repressed the survival of CSCs and the protein expression of NDUFA4L2. CHIP assay showed that HIF-1α regulated the survival of CSCs by augmenting the combination of HIF-1α and NDUFA4L2's HRE. Knockdown of NDUFA4L2 reversed the role of hypoxia in the survival of CSCs. Taken together, hypoxia promotes the viability of CSCs in serum-free medium by HIF-1α/NDUFA4L2 signaling pathway.
成年哺乳动物的心脏在心肌细胞损伤后不会再生，这主要是由心肌病的严重和持续影响引起的。最近，一些研究报告称，哺乳动物的心脏在低氧环境下可以再生。然而，哺乳动物心脏能够再生的机制尚不清楚。在这里，我们使用心脏干细胞（CSCs）在低氧环境下的无血清培养基中种植，以了解 HIF1α/NDUFA4L2 在调节低氧缓解细胞凋亡中的作用机制。我们的结果表明，低氧可以减轻 CSCs 的凋亡。低氧抑制了 cleaved-caspase3 的水平，并刺激了稳定的 HIF-1α 的表达。DMOG 促进 CSCs 的存活和 NDUFA4L2 的蛋白表达。2-ME 抑制了 CSCs 的存活和 NDUFA4L2 的蛋白表达。CHIP 分析表明，HIF-1α 通过增强 HIF-1α 和 NDUFA4L2 的 HRE 的结合来调节 CSCs 的存活。NDUFA4L2 的敲低逆转了低氧对 CSCs 存活的作用。总之，低氧通过 HIF-1α/NDUFA4L2 信号通路促进无血清培养基中 CSCs 的活力。
