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首页> 外文期刊>Current Chinese Science. >Artesunate Reverses Clozapine-induced Lipid Metabolism Disorder in BRL-3A Cells by Effecting AMPK Pathway
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Artesunate Reverses Clozapine-induced Lipid Metabolism Disorder in BRL-3A Cells by Effecting AMPK Pathway

机译：青蒿琥酯通过影响 AMPK 通路逆转氯氮平诱导的 BRL-3A 细胞脂质代谢紊乱

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Background: Clozapine (CLZ) is the only registered drug for treatment-resistant schizophrenia and also associated with metabolic abnormalities, including obesity, hyperglycemia, and dyslipidemia. Objective: This study aimed to examine the effects of CLZ on lipid metabolism in BRL-3A cells, measure possible effects of artesunate (ART) on the CLZ-induced alterations in lipid metabolism, and explore the molecular mechanism underlying the CLZ- and ART-induced changes in the cells. Methods: BRL-3A cells were cultured in DMEM at different conditions in the CLZ experiment (20, 30, or 40 gM CLZ), CLZ-ART experiment (40 gM CLZ followed by ART at 5, 10, or 20 gM), or CLZ-ART experiment consisting DMSO, CLZ, CLZ+ART, and ART groups. In addition to cell viability assessment, triglyceride, total and free cholesterol in BRL-3A cells were measured by biochemistry analyses, and levels of lipid metabolism-related genes and relevant proteins were evaluated by means of quantitative PCR and Western blot. Results: CLZ in the used range increased levels of free and total cholesterol in BRL-3A while up-regulated mRNA levels of HMGCR, PPARα, and PPARγ. Moreover, the treatment increased SREBP-1c mRNA and protein levels in the cells, although it showed no impact on the phosphorylation of AMPK. ART treatment following CLZ exposure reversed the CLZ-induced high levels of free and total cholesterol in BRL-3A. ART effectively ameliorated or normalized the CLZ-induced changes in the HMGCR, PPARα, PPARγ, and SREBP-1c. Furthermore, ART increased AMPK phosphorylation in BRL-3A. Conclusion: These results suggest that ART exerts a cholesterol-lowering effect in BRL-3A by affecting the AMPK/SREBP-1c/PPARγ pathway.
机译：背景:氯氮平(CLZ)是唯一的注册药物难治性精神分裂症和也与代谢异常有关,包括肥胖、高血糖和血脂异常检查CLZ在脂质代谢的影响BRL-3A细胞,可能测量的影响青蒿琥酯(ART) CLZ-induced改变在脂类代谢,探索分子如今CLZ和机制细胞的变化。在DMEM培养不同的条件CLZ实验(20、30或40通用CLZ), CLZ-ART实验(40通用CLZ其次是艺术在5、10日20 gM)或CLZ-ART实验组成DMSO溶液,CLZ CLZ +艺术和艺术团体。可行性评估、甘油三酯、总免费BRL-3A细胞胆固醇测定生物化学分析,和脂质水平代谢相关的基因和相关的蛋白质评估通过定量PCR和吗免疫印迹。的自由和总胆固醇水平增加BRL-3A mRNA表达而上调HMGCR的水平,PPARα,PPARγ。SREBP-1c信使rna和蛋白质含量增加细胞,尽管它没有影响AMPK的磷酸化。CLZ逆转CLZ-induced高水平的敞口BRL-3A自由和总胆固醇。有效地改善或规范化CLZ-induced HMGCR的变化,PPARα,PPARγ,和SREBP-1c。在BRL-3A磷酸化。结果表明,施加一个艺术在BRL-3A降胆固醇效果影响AMPK / SREBP-1c PPARγ途径。

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