Journal Article

Folate receptor and human reduced folate carrier expression in HepG2 cell line exposed to fumonisin B<sub>1</sub> and folate deficiency

Afif M. Abdel Nour, Diana Ringot, Jean-Louis Guéant and Abalo Chango

in Carcinogenesis

Volume 28, issue 11, pages 2291-2297
Published in print November 2007 | ISSN: 0143-3334
Published online July 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm149
Folate receptor and human reduced folate carrier expression in HepG2 cell line exposed to fumonisin B1 and folate deficiency

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Fumonisin B1 (FB1) induces apoptosis and decreases the cellular uptake of 5-methyltetrahydrofolate. Two folate transporters (folate receptor, FR, and Reduced Folate Carrier, hRFC1) are involved in the cell uptake of folate. We aimed to study whether FB1 modifies the expression of the FR and the hRFC1 and whether its apoptotic effect is influenced by folate. Incubation of HepG2 cells with FB1 induced apoptosis in concentration and time-dependent manner in complete medium (experimental control medium, ECM), as well as in folate-depleted medium (FDM). FDM increased the toxicity of FB1 as the cells developed apoptosis within 24 h at 1 μM of FB1 instead of 100 μM in ECM. Whereas FR protein expression in cells grown in ECM was significantly inhibited after apoptosis event, protein expression of the hRFC1 was rather increased. The hrfc1 transcription was decreased in the treated cells. Under folate-deficient conditions, dramatic changes were observed on both transcriptional and post-transcriptional expression of the two transporters. FDM alone reduced FR protein expression by 12 ± 2% and 43 ± 1% at 48 and 72 h, respectively. The 5-methytetrahydrofolate attenuates apoptosis in a greater extent than the folic acid. However, its effects in preventing decrease of both folate transporters have not been observed. In conclusion, this study shows that the changes in the expression of FR after FB1 addition are probably a consequence of the FB1 toxicity. The response to FB1 by HepG2 cell lines is influenced by folate status and by folate form. 5-Methyltetrahydrofolate appears to be more effective in preventing apoptosis than folic acid.

Journal Article.  5534 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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