Effect of fumonisin B1 on protein and lipid synthesis in primary rat hepatocytes.
Journal Title: Food and Chemical Toxicology - Year 1996, Vol 34, Issue 4
Abstract
The effect of fumonisin B1 (FB1) on protein and lipid synthesis was evaluatedin primary rat hepatocytes. FB1 did not affect incorporation of [3H]leucine into hepatocytes at eithernon-toxic (150 microM) or cytotoxic (500 microM) concentrations indicating that protein synthesis wasnot affected. However, FB1 significantly (P < 0.01 to P < 0.0001) inhibited incorporation of [14C]palmiticacid into hepatocyte cultures implying that lipid synthesis was altered. Incorporation of the radiolabelwas significantly (P < 0.05 to P < 0.0001) lowered in triacylglycerol (TAG) and sphingomyelin fractionsand increased in phosphatidylcholine (PC) and phosphatidylethanolamine (PEA) in both FB1 concentrations.The incorporation pattern of [14C]palmitic acid closely resembles the changes in phospholipid levelsin the treated cells. The sphingolipid, sphinganine (Sa), was significantly (P < 0.0001) increased intreated cells but there was no significant difference between the toxic and non-toxic dose levels implyingthat the increased Sa level alone is not responsible for the in vitro toxicity. FB1 significantly (P< 0.01 to P < 0.001) decreased the level of free cholesterol within the cell, resulting in an increasedPC:cholesterol ratio suggesting a more rigid membrane structure. Subsequent studies on the fatty acid(FA) profiles in PC and the neutral lipid, TAG, indicated that FB1 significantly (P < 0.05 to P < 0.0001)increased the levels of the polyunsaturated FAs C18:2n-6 and C20:4n-6 at both concentrations. The FB1-inducedchanges to cellular membranes, specifically those related to FA changes in the major membrane phospholipids,and the altered FA content of the hepatocytes are likely to be key events in explaining the cytotoxiceffects and altered growth responses induced by fumonisins in primary hepatocytes.
Authors and Affiliations
W C Gelderblom, C M Smuts, S Abel, S D Snyman, M E Cawood, L van der Westhuizen
Keywords
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