Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia.
Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia.
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丙泊酚后处理通过上调叉头转录因子改善高血糖下缺氧/复氧诱导的 H9c2 细胞凋亡和自噬
DOI：
10.1186/s40779-021-00353-0
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发表时间：
2021-11-10
影响因子：
21.1
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Han RH;Huang HM;Han H;Chen H;Zeng F;Xie X;Liu DY;Cai Y;Zhang LQ;Liu X;Xia ZY;Tang J
异丙酚是一种具有抗氧化特性的静脉麻醉剂，在缺血再灌注开始时立即给予异丙酚(异丙酚后处理，P-PostC)已被证明对缺血再灌注损伤具有心脏保护作用，但其潜在机制仍不完全清楚。据报道，FoxO转录因子在氧化应激诱导的细胞损伤过程中发挥关键作用，激活心肌细胞生存信号，并参与低氧后处理介导的神经保护，但FoxO在心脏特别是高糖条件下的后处理保护中的作用尚不清楚。大鼠心脏来源的H9c2细胞暴露于高糖(HG)48小时(H)，然后在没有或存在不同浓度异丙酚(P-PostC)的后处理条件下进行缺氧/复氧(H/R，由8小时的缺氧和12小时的复氧组成)。在确定了异丙酚的最佳浓度后，H9c2细胞在没有或存在FoxO1或FOXO3a基因沉默的情况下受到H/R和P-PostC的影响，以探讨它们在P-PostC介导的保护高血糖下细胞凋亡和自噬细胞死亡中的作用。结果表明，HG加或不加H/R使H9c2细胞存活率下降、乳酸脱氢酶漏出增加和ROS生成增加，这些作用均被异丙酚(P-PostC)显著逆转，尤其是在25µm ol/L(P25)时(均P <； 0.05，NC vs HG；HG vs HG + HR；HG + HR + P12.5或HG + HR + P25或HG + HR + P50 vs HG + HR)。此外，我们还发现，异丙酚(P25)减少了H9c2细胞的凋亡和自噬，同时伴随着FoxO1和FoxO3a表达的增加(All P <； 0.05，HG + HR + P25 vs HG + HR)。阻断FOXO1或FOXO3a(All P <； 0.05，HG + HR + P25 vs.HG + HR + P25 + siRNA-1或HG + HR + P25 + siRNA-5)可逆转异丙酚(P25)对H/R损伤的保护作用。结论：异丙酚后处理可通过上调高血糖下FoxO1和FOXO3a的表达，减轻H/R损伤所致的H9c2细胞的凋亡和自噬。
Administration of propofol, an intravenous anesthetic with antioxidant property, immediately at the onset of post-ischemic reperfusion (propofol postconditioning, P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion injury, while the underlying mechanism remains incompletely understood. The FoxO transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection, however, the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown. Rat heart-derived H9c2 cells were exposed to high glucose (HG) for 48 h (h), then subjected to hypoxia/reoxygenation (H/R, composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol (P-PostC) at the onset of reoxygenation. After having identified the optical concentration of propofol, H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia. The results showed that HG with or without H/R decreased cell viability, increased lactate dehydrogenase (LDH) leakage and the production of reactive oxygen species (ROS) in H9c2 cells, all of which were significantly reversed by propofol (P-PostC), especially at the concentration of 25 µmol/L (P25) (all P < 0.05, NC vs. HG; HG vs. HG + HR; HG + HR + P12.5 or HG + HR + P25 or HG + HR + P50 vs. HG + HR). Moreover, we found that propofol (P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression (all P < 0.05, HG + HR + P25 vs. HG + HR). The protective effects of propofol (P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a (all P < 0.05, HG + HR + P25 vs. HG + HR + P25 + siRNA-1 or HG + HR + P25 + siRNA-5). It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.
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DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
影响因子：
10.8
作者：
Javadov, SA;Lim, KHH;Halestrap, AP
通讯作者：
Halestrap, AP
DOI：
10.1152/ajpheart.00783.2002
发表时间：
2003-06-01
影响因子：
4.8
作者：
Hochhauser, E;Kivity, S;Vidne, BA
通讯作者：
Vidne, BA
DOI：
10.1073/pnas.161120198
发表时间：
2001-08-14
影响因子：
11.1
作者：
Condorelli, G;Roncarati, R;Croce, CM
通讯作者：
Croce, CM
影响因子：
4
作者：
Jin, Yong Chun;Kim, WooYeol;Chang, Ki Churl
通讯作者：
Chang, Ki Churl