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Zeng, Yan; Du, William W; Wu, Yingya; Yang, Zhenguo; Awan, Faryal Mehwish; Li, Xiangmin; Yang, Weining; Zhang, Chao; Yang, Qi; Yee, Albert; Chen, Yu; Yang, Fenghua; Sun, Huan; Huang, Ren; Yee, Albert J; Li, Ren-Ke; Wu, Zhongkai; Backx, Peter H; Yang, Burton B
Theranostics, 01/2017, Letnik: 7, Številka: 16Journal Article
As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified . Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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