Purine Nucleotide Alterations in Tumoral Cell Lines Maintained with Physiological Levels of Folic Acid
Cano-Estrada, Claudia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
de Benito-Gómez, Lidia (Hospital Universitari de Bellvitge)
Escudero-Ferruz, Paula (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ontiveros, Neus (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Iglesias-Serret, Daniel (Universitat de Vic - Universitat Central de Catalunya)
López Riba, José M. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2023
Resum:	Most cancer cells have an increased synthesis of purine nucleotides to fulfil their enhanced division rate. The de novo synthesis of purines requires folic acid in the form of N 10 -formyltetrahydrofolate (10-formyl-THF). However, regular cell culture media contain very high, non-physiological concentrations of folic acid, which may have an impact on cell metabolism. Using cell culture media with physiological levels of folic acid (25 nM), we uncover purine alterations in several human cell lines. HEK293T, Jurkat, and A549 cells accumulate 5'-aminoimidazole-4-carboxamide ribonucleotide (ZMP), an intermediary of the de novo biosynthetic pathway, at physiological levels of folic acid, but not with the artificially high levels (2200 nM) present in regular media. Interestingly, HEK293T and Jurkat cells do not accumulate high levels of ZMP when AICAr, the precursor of ZMP, is added to medium containing 2200 nM folate; instead, ATP levels are increased, suggesting an enhanced de novo synthesis. On the other hand, HeLa and EHEB cells do not accumulate ZMP at physiological levels of folic acid, but they do accumulate in medium containing AICAr plus 2200 nM folate. Expression of SLC19A1, which encodes the reduced folate carrier (RFC), is increased in HEK293T and Jurkat cells compared with HeLa and EHEB, and it is correlated with the total purine nucleotide content at high levels of folic acid or with ZMP accumulation at physiological levels of folic acid. In conclusion, tumoral cell lines show a heterogenous response to folate changes in the media, some of them accumulating ZMP at physiological levels of folic acid. Further research is needed to clarify the ZMP downstream targets and their impact on cell function.
Ajuts:	Agencia Estatal de Investigación PID2020-113124RB-C21
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	AICAR ; Cancer ; Folic acid ; Nucleotides ; Purines ; SLC19A1 ; ZMP
Publicat a:	International journal of molecular sciences, Vol. 24 (august 2023) , ISSN 1422-0067

DOI: 10.3390/ijms241612573
PMID: 37628755

18 p, 1.9 MB

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