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鸡骨提取物对K562细胞系代谢和线粒体功能的影响

Effect of Chicken Bone Extracts on Metabolic and Mitochondrial Functions of K562 Cell Line.

作者信息

Pacelli Consiglia, Di Cerbo Alessandro, Lecce Lucia, Piccoli Claudia, Canello Sergio, Guidetti Gianandrea, Capitanio Nazzareno

机构信息

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy.

出版信息

Pharmaceuticals (Basel). 2020 Jun 2;13(6):114. doi: 10.3390/ph13060114.

Abstract

BACKGROUND

Tetracyclines' use in intensive animal farming has raised some concerns regarding the biosafety for humans. Increasing evidences have revealed the presence of these drugs in processed animal by-products, such as bone, throughout the food chain. A potential off-target of tetracyclines is the bacterial-like mitochondrial translational machinery, thereby causing proteostatic alterations in mitochondrial DNA-encoded components of the oxidative phosphorylation system.

METHODS

The Seahorse methodology, confocal microscopy imaging of mitochondrial potential and reactive oxygen species, and q-RT-PCR analysis of the expression of genes involved in mitochondrial biogenesis and mitophagy were carried out on human lymphoblast derived K562 cell line challenged with bone powder derived from chicken treated with or without oxytetracycline and pure oxytetracycline.

RESULTS

A complex dose-dependent profile was attained with a low dosage of bone powder extracts causing a metabolic adaptation hallmarked by stimulation of the mitochondrial respiration and enhanced expression of mitochondriogenic factors in particular in cells challenged with oxytetracycline-free bone extract. Conversely, a higher dosage of bone powder extracts, regardless of their source, caused a progressive inhibition of mitochondrial respiration and glycolysis, ultimately leading to cell death. No significant effects of the pure oxytetracycline were observed.

CONCLUSION

Bone powder, regardless of chicken treatment, contains and releases factors/chemicals responsible for the observed effects on energy metabolism. Quantitative differential effects appear to depend on biochemical alterations in the bone matrix caused by antibiotics rather than antibiotics themselves.

摘要

背景

四环素在集约化动物养殖中的使用引发了人们对其对人类生物安全性的一些担忧。越来越多的证据表明,这些药物在整个食物链的加工动物副产品(如骨头)中都有存在。四环素的一个潜在脱靶效应是类细菌线粒体翻译机制,从而导致氧化磷酸化系统中线粒体DNA编码成分的蛋白质稳态改变。

方法

对源自人淋巴母细胞的K562细胞系进行了海马分析、线粒体电位和活性氧的共聚焦显微镜成像,以及对用土霉素处理或未处理的鸡的骨粉和纯土霉素刺激的细胞中线粒体生物发生和线粒体自噬相关基因表达的q-RT-PCR分析。

结果

低剂量骨粉提取物呈现出复杂的剂量依赖性特征,导致代谢适应,其标志是线粒体呼吸的刺激和线粒体生成因子表达的增强,特别是在用不含土霉素的骨提取物刺激的细胞中。相反,无论来源如何,较高剂量的骨粉提取物都会导致线粒体呼吸和糖酵解的逐渐抑制,最终导致细胞死亡。未观察到纯土霉素有显著影响。

结论

无论鸡的处理方式如何,骨粉都含有并释放出对观察到的能量代谢影响负责的因子/化学物质。定量差异效应似乎取决于抗生素引起的骨基质生化改变,而非抗生素本身。

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