艾氯胺酮抑制心肌细胞自噬,通过下调瞬时受体电位香兰素1表达,抑制Ca2+/CaMKKβ/AMPK/mTOR通路,减轻心肌细胞缺氧/再氧化损伤。

IF 2 4区 医学 Q3 PHYSIOLOGY
Journal of Physiology and Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-05-05 DOI:10.26402/jpp.2025.2.05
Y Zhang, Q M Lu, H C Hu, C C Yang, Q H Zhao
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引用次数: 0

摘要

本研究旨在通过瞬时受体电位香草酸1型(TRPV1)/ Ca2+/钙调素依赖性蛋白激酶β (CaMKKβ)/单磷酸腺苷(AMP)活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)途径阻断自噬,确定艾氯胺酮(ESK)对心肌细胞缺氧/再氧化(H/R)损伤的影响。H9c2心肌细胞缺氧4 h,复氧6 h,缺氧前用ESK (30 μg/ml)预处理H9c2细胞。用干扰TRPV1或CaMKKβ的质粒载体转染H9c2细胞,RT-qPCR验证转染成功。MTT法检测细胞活力;流式细胞术检测细胞凋亡;采用荧光染料Fluo-3 AM/Pluronic F127检测细胞内Ca2+浓度([Ca2+]i), Western blot检测LC3-I、LC3-II、Beclin-1和CaMKKβ/AMPK/ mtor相关蛋白。结果:ESK处理抑制H/ r诱导的细胞损伤、细胞自噬和[Ca2+]i升高。诱导自噬或[Ca2+]i升高会减弱ESK对H/ r诱导的细胞损伤的改善作用。我们得出结论,esk诱导的对H/R损伤的保护作用,并降低了对CaMKKβ/AMPK/mTOR通路的影响。ESK通过TRPV1/Ca2+/CaMKKβ/AMPK/mTOR通路阻碍自噬,从而减轻H/R心肌细胞损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of autophagy by esketamine attenuates hypoxia/reoxygenation injury in cardiomyocytes via inhibition of Ca2+/CaMKKβ/AMPK/mTOR pathway by down-regulation of transient receptor potential vanilloid 1 expression.

This research sought to determine the influence of esketamine (ESK) on hypoxia/reoxygenation (H/R) injury in cardiomyocytes by blocking autophagy via the transient receptor potential vanilloid type 1 (TRPV1)/ Ca2+/ calmodulin-dependent protein kinase β (CaMKKβ)/ adenosine monophosphate (AMP)-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) pathway. H9c2 cardiomyocytes were hypoxic for 4 h and reoxygenated for 6 h. H9c2 cells were pretreated with ESK (30 μg/ml) before hypoxia. H9c2 cells were transfected with plasmid vectors that interfered with TRPV1 or CaMKKβ, and the success of the transfections was verified by RT-qPCR. Cell viability was detected by MTT assay; apoptosis was detected by flow cytometry; intracellular Ca2+ concentration ([Ca2+]i) was assessed using fluorescent dye Fluo-3 AM/Pluronic F127, and LC3-I, LC3-II, Beclin-1, and CaMKKβ/AMPK/mTOR-related proteins were detected by Western blot. In results: ESK treatment inhibited H/R-induced cell injury, cellular autophagy, and [Ca2+]i elevation. Induction of autophagy or [Ca2+]i elevation attenuated the ameliorative effect of ESK on H/R-induced cell injury. Upregulating TRPV1 attenuated We conclude that ESK-induced protection against H/R injury, as well as reduced the effect on the CaMKKβ/AMPK/mTOR pathway. ESK attenuates H/R cardiomyocyte injury by hindering autophagy through the TRPV1/Ca2+/CaMKKβ/AMPK/mTOR pathway.

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来源期刊
CiteScore
4.00
自引率
22.70%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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