Premium
Glutamine Deprivation Hinders the Proliferation of Human Oligodendroglioma Cells Negative for Glutamine Synthetase
Author(s) -
Ottaviani Laura,
Chiu Martina,
Bianchi Massimiliano,
Bussolati Ovidio
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb447
Subject(s) - glutamine , glutamine synthetase , extracellular , cell culture , western blot , microbiology and biotechnology , biology , intracellular , enzyme , biochemistry , blot , amino acid , gene , genetics
Negativity for the astroglial marker Glutamine Synthetase (GS) is an histological hallmark of human oligodendrogliomas (OL). Given that GS accounts for the intracellular synthesis of glutamine (Gln), we hypothesized that OL cells are strictly dependent upon the availability of external Gln. To test this hypothesis, we compared the effects of several treatments on two human oligodendroglioma cell lines, HOG and Hs683, and two GS‐positive glioblastoma cells, U87 and U373 cells. Compared to HOG and Hs683 cells, the abundance of the GS‐encoding GLUL mRNA was more than 1000‐fold higher in U373 cells, while the expression of GS protein was undetectable in Western Blot in both OL lines. HOG and Hs683 cells were more sensitive than glioblastoma cells to reduced availability of extracellular Gln caused by (1) the glutaminolytic enzyme L‐Asparaginase (ASNase) from Erwinia chrysanthemi (IC 50 values < 0.1 U/ml); (2) the incubation at decreasing levels of extracellular Gln; (3) the incubation in the presence of competitive inhibitors of sodium‐dependent transporters for Gln. In particular, the viability of both OL cell lines was markedly affected by MeAIB, an inhibitor of the SNAT transporters of the SLC38 gene family, while glioblastoma cells were substantially unaffected. Moreover, both OL cell lines exhibited higher levels of expression of the mRNA for the SNAT1 transporter than glioblastoma cells. Thus, OL cells are markedly dependent on extracellular Gln suggesting that GS negativity may constitute a marker of sensitivity to treatments aimed at reducing the availability of the amino acid.