Differential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1-induced cytotoxic effects in vitro.
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.
Biomedical Research and Innovation Platform, South African Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa. Electronic address: sylvia.riedel@mrc.ac.za.
S
S
Riedel
Mycotoxicology and Chemoprevention Research Group, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa. Electronic address: abels@cput.ac.za.
S
S
Abel
Mycotoxicology and Chemoprevention Research Group, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa. Electronic address: burgerh@cput.ac.za.
H-M
HM
Burger
Oxidative Stress Research Centre, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa. Electronic address: vanderwesthuizenL@cput.ac.za.
L
L
van der Westhuizen
Biostatistics Unit, South African Medical Research Council, PO Box 19070, Tygerberg, South Africa. Electronic address: sonja.swanevelder@mrc.ac.za.
S
S
Swanevelder
Mycotoxicology and Chemoprevention Research Group, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa; Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa. Electronic address: gelderblomw@cput.ac.za.
W C A
WC
Gelderblom
D000818:Animals; D045744:Cell Line, Tumor; D004351:Drug Resistance; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D037341:Fumonisins / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats
D005231:Fatty Acids, Unsaturated; D037341:Fumonisins; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; C056933:fumonisin B1
Apoptosis; Cell proliferation; Cytotoxicity; Fatty acids; Fumonisin B1; Lipids; Resistance