脂质代谢的差异调节作为体外细胞对伏马菌素B1诱导的细胞毒性作用抗性的模型。

Differential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1-induced cytotoxic effects in vitro.

作者信息

Riedel S, Abel S, Burger H-M, van der Westhuizen L, Swanevelder S, Gelderblom W C A

机构信息

Biomedical Research and Innovation Platform, South African Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa.

Mycotoxicology and Chemoprevention Research Group, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2016 Jun;109:39-51. doi: 10.1016/j.plefa.2016.04.006. Epub 2016 Apr 22.

DOI:10.1016/j.plefa.2016.04.006

PMID:27269712

Abstract

Differential sensitivity of primary hepatocytes and Chang cells to the cancer promoter fumonisin B1 (FB1)-induced cytotoxic effects were investigated in relation to changes in membrane lipid distribution. In contrast to primary hepatocytes, Chang cells were resistant to FB1-induced cytotoxic effects. This was associated with a high cholesterol (Chol) and sphingomyelin (SM) and low phosphatidylcholine (PC) content, resulting in a significant (P<0.05) decrease in phosphatidylethanolamine (PE)/PC ratio, increased Chol/total phosphoglyceride (TPG) ratios and low total polyunsaturated fatty acids (PUFA) content in PC and PE, suggesting a more rigid membrane structure. High levels of C18:1 and reduced polyunsaturated fatty acid (PUFA) levels are likely to provide selective resistance to FB1-induced oxidative stress. FB1-associated lipid changes included decreases in SM and Chol, increases in sphinganine (Sa) and PE with the increases in key saturated, monounsaturated, and PUFAs in PE as key role players in the differential responses to FB1-induced cell growth responses in cells.

摘要

研究了原代肝细胞和Chang细胞对癌症启动剂伏马菌素B1（FB1）诱导的细胞毒性作用的差异敏感性，并探讨了其与膜脂分布变化的关系。与原代肝细胞不同，Chang细胞对FB1诱导的细胞毒性作用具有抗性。这与高胆固醇（Chol）和鞘磷脂（SM）含量以及低磷脂酰胆碱（PC）含量有关，导致磷脂酰乙醇胺（PE）/PC比值显著降低（P<0.05），Chol/总磷酸甘油酯（TPG）比值升高，PC和PE中的总多不饱和脂肪酸（PUFA）含量降低，表明膜结构更僵硬。高水平的C18:1和降低的多不饱和脂肪酸（PUFA）水平可能为FB1诱导的氧化应激提供选择性抗性。与FB1相关的脂质变化包括SM和Chol减少，鞘氨醇（Sa）和PE增加，同时PE中关键的饱和、单不饱和和多不饱和脂肪酸增加，这些脂肪酸在细胞对FB1诱导的细胞生长反应的差异响应中起关键作用。