Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression
Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression
复制标题
低剂量尼古丁通过上调HO-1表达促进心肌细胞自噬
DOI：
10.1016/j.bbrc.2019.11.086
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发表时间：
2020
影响因子：
3.1
通讯作者：
Han Yaling
中科院分区：
文献类型：
--
作者：
Xing Ruinan;Cheng Xiaoli;Qi Yanping;Tian Xiaoxiang;Yan Chenghui;Liu Dan;Han Yaling
尼古丁作为香烟成瘾的主要成分，已被报道在某些病理过程中起保护作用。据报道，烟碱乙酰胆碱受体的激活也具有心脏保护作用。因此，在我们的研究中，我们研究了尼古丁对心肌细胞自噬的影响和机制，以及尼古丁是否保护心肌细胞免受棕榈酸（PA）损伤。结果表明，低剂量尼古丁促进新生小鼠心肌细胞自噬，加快自噬流量，抑制心肌细胞凋亡;高剂量尼古丁抑制自噬，促进心肌细胞凋亡。此外，低剂量尼古丁上调血红素氧合酶-1（HO-1）的表达，并敲低HO-1取消尼古丁对NMCs自噬和凋亡的影响。α 7-nAChR阻断剂（methyllycaconitine citrate，MLA）可抑制HO-1的表达及尼古丁对NMCs自噬和凋亡的影响。此外，低剂量尼古丁改善了棕榈酸（PA）诱导的NMCs自噬抑制和凋亡增加，这些作用可通过敲低HO-1逆转。总之，我们的数据表明低剂量尼古丁通过上调HO-1促进心肌细胞自噬并抑制心肌细胞凋亡。
Nicotine as a major component of addiction in cigarettes has been reported to play protective roles in some pathological processes. It is reported that activation of the nicotinic acetylcholine receptor also has a cardioprotective effect. Thus, in our study, we investigated the effect and mechanism of nicotine on the autophagy of cardiomyocytes, and whether nicotine protects cardiomyocytes against palmitic acid (PA) injury. The results indicated that low-dose nicotine promoted neonatal mouse cardiac myocytes (NMCMs) autophagy and accelerated autophagic flux while inhibiting NMCMs apoptosis, but high-dose nicotine inhibited autophagy and promoted apoptosis. Moreover, low-dose nicotine upregulated heme oxygenase-1 (HO-1) expression and knocking down HO-1 abolished the effects of nicotine on the autophagy and apoptosis of NMCMs. Methyllycaconitine citrate (α7-nAChR blocker, MLA) inhibited HO-1 expression and the effects of nicotine on autophagy and apoptosis of NMCMs. Furthermore, low-dose nicotine improved the inhibited autophagy and increased apoptosis induced by palmitic acid (PA) in NMCMs and these effects were reversed by knocking down HO-1. In conclusion, our data suggested that low-dose nicotine promoted autophagy and inhibited apoptosis of cardiomyocytes by upregulating HO-1.