Propofol Upregulates MicroRNA-30b to Inhibit Excessive Autophagy and Apoptosis and Attenuates Ischemia/Reperfusion Injury In Vitro and in Patients.
Propofol Upregulates MicroRNA-30b to Inhibit Excessive Autophagy and Apoptosis and Attenuates Ischemia/Reperfusion Injury In Vitro and in Patients.
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异丙酚上调 MicroRNA-30b 以抑制过度自噬和细胞凋亡，并减轻体外和患者的缺血/再灌注损伤
DOI：
10.1155/2022/2109891
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发表时间：
2022
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Lu Z;Shen J;Chen X;Ruan Z;Cai W;Cai S;Li M;Yang Y;Mo J;Mo G;Lu Y;Tang J;Zhang L
有证据表明，异丙酚通过抑制缺氧/复氧（H/R）诱导的过度自噬来保护细胞。此前，我们在全基因组microRNA图谱分析中发现，在存在或不存在丙泊酚缺氧后治疗（P-PostH）的H/R过程中，一些自噬相关microRNA发生了显著改变，但这些microRNA在P-PostH中如何工作仍是未知数。在这里，我们发现，这些microRNA之一，microRNA-30 b（miR-30 b），在人脐静脉内皮细胞（HUVECs）下调H/R处理，但显着上调100 M丙泊酚H/R处理后。miR-30 b在心脏直视手术患者中显示出类似的变化。通过双荧光素酶检测，我们发现Beclin-1是miR-30 b的直接靶点。这一结论也得到了miR-30 b敲低或过表达的支持。进一步的研究表明，miR-30 b抑制H/R诱导的自噬激活。miR-30 b的过表达或敲低调控体外自噬相关蛋白基因的表达。为了阐明丙泊酚在抑制自噬中的特定作用，并区分自噬的诱导和自噬通量的损伤，我们使用了巴弗洛霉素A1。与单纯巴弗洛霉素A1组相比，丙泊酚联合巴弗洛霉素A1组在缺氧复氧后LC 3-II水平降低。此外，转染Ad-mCherry-GFP-LC 3b的HUVECs证实了miR-30 b对自噬通量的抑制作用。最后，我们发现miR-30 b能够在H/R条件下增加细胞活力，部分模拟丙泊酚通过增强miR-30 b和靶向Beclin-1抑制自噬的保护作用。因此，我们认为丙泊酚通过靶向Beclin-1上调miR-30 b抑制H/R条件下过度的自噬。因此，我们的研究结果揭示了异丙酚在麻醉过程中保护作用的新机制。临床试验注册号。本试验注册于ChiCTR-IPR-14005470。试验注册名称：丙泊酚上调MicroRNA-30 b以抑制Beclin-1并抑制过度自噬和凋亡。
Evidence reveals that propofol protects cells via suppressing excessive autophagy induced by hypoxia/reoxygenation (H/R). Previously, we found in a genome-wide microRNA profile analysis that several autophagy-related microRNAs were significantly altered during the process of H/R in the presence or absence of propofol posthypoxia treatment (P-PostH), but how these microRNAs work in P-PostH is still largely unknown. Here, we found that one of these microRNAs, microRNA-30b (miR-30b), in human umbilical vein endothelial cells (HUVECs) was downregulated by H/R treatment but significantly upregulated by 100 M propofol after H/R treatment. miR-30b showed similar changes in open heart surgery patients. By dual-luciferase assay, we found that Beclin-1 is the direct target of miR-30b. This conclusion was also supported by knockdown or overexpression of miR-30b. Further studies showed that miR-30b inhibited H/R-induced autophagy activation. Overexpression or knockdown of miR-30b regulated autophagy-related protein gene expression in vitro. To clarify the specific role of propofol in the inhibition of autophagy and distinguish the induction of autophagy from the damage of autophagy flux, we used bafilomycin A1. LC3-II levels were decreased in the group treated with propofol combined with bafilomycin A1 compared with the group treated with bafilomycin A1 alone after hypoxia and reoxygenation. Moreover, HUVECs transfected with Ad-mCherry-GFP-LC3b confirmed the inhibitory effect of miR-30b on autophagy flux. Finally, we found that miR-30b is able to increase the cellular viability under the H/R condition, partially mimicking the protective effect of propofol which suppressed autophagy via enhancing miR-30b and targeting Beclin-1. Therefore, we concluded that propofol upregulates miR-30b to repress excessive autophagy via targeting Beclin-1 under H/R condition. Thus, our results revealed a novel mechanism of the protective role of propofol during anesthesia. Clinical Trial Registration Number. This trial is registered with ChiCTR-IPR-14005470. The name of the trial register: Propofol Upregulates MicroRNA-30b to Repress Beclin-1 and Inhibits Excessive Autophagy and Apoptosis.
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自噬体生物发生分解为不同的成核和膨胀步骤。
DOI：
10.1083/jcb.151.5.1025
发表时间：
2000-11-27
期刊：
The Journal of cell biology
影响因子：
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作者：
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影响因子：
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