Induction of gadd153 mRNA by nutrient deprivation is overcome by glutamine

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The growth arrest and DNA damage-inducible (gadd) genes are co-ordinately activated by a variety of genotoxic agents and/or growth-cessation signals. The regulation of gadd153 mRNA was investigated in renal proximal tubular epithelial cells (LLC-PK1) cultured in a nutrient- and serum-deprived medium. The addition of glutamine alone to LLC-PK1 cells cultured in Earl's balanced salt solution (EBSS) is sufficient to suppress gadd153 mRNA expression, and the removal of only glutamine from Dulbecco's modified Eagle's medium (DMEM) is also sufficient to induce gadd153 mRNA expression. Consistent with these findings, the inhibition of glutamine utilization with acivicin and 6-diazo-5-oxo-L-norleucine (DON) in cells grown in a glutamine-containing medium effectively induces gadd153 expression. Glutamine can be used as an energy source in cultured mammalian cells. However, it is unlikely that deficits in cellular energy stores (ATP) are coupled to gadd153 mRNA expression, because concentrations of ATP, UTP and GTP are all elevated in EBSS-exposed cells, and the addition of α-oxoglutarate to cells grown in EBSS has no effect on gadd153 mRNA expression. In contrast, concentrations of CTP decline substantially in EBSS and glutamine-deprived DMEM-cultured cells. Glutamine also serves as a precursor for the synthesis of protein and DNA. The addition of glutamine to cells grown in EBSS partly restores CTP concentrations. The addition of pyrimidine ribonucleosides (cytidine and uridine) to LLC-PK1 cells also restores CTP concentrations, in a manner commensurate with their relative abilities to overcome gadd153 expression. Finally, glutamine does not completely suppress DNA damage-induced gadd153 expression, suggesting that multiple signalling pathways lead to the expression of gadd153 mRNA under conditions of nutrient deprivation and DNA damage.

Original languageEnglish (US)
Pages (from-to)225-231
Number of pages7
JournalBiochemical Journal
Volume341
Issue number1
DOIs
StatePublished - Jul 1 1999
Externally publishedYes

Fingerprint

Glutamine
Nutrients
Food
Messenger RNA
Cytidine Triphosphate
Salts
Cells
LLC-PK1 Cells
DNA Damage
Eagles
DNA
acivicin
Cultured Cells
Diazooxonorleucine
Adenosine Triphosphate
Ribonucleosides
Ketoglutaric Acids
Cytidine
Uridine Triphosphate
Protein Precursors

Keywords

  • CTP
  • Glutamine
  • Growth arrest
  • LLC-PK1 cells
  • Nucleotide depletion

ASJC Scopus subject areas

  • Biochemistry

Cite this

Induction of gadd153 mRNA by nutrient deprivation is overcome by glutamine. / Huang, Qihong; Lau, Serrine; Monks, Terrence.

In: Biochemical Journal, Vol. 341, No. 1, 01.07.1999, p. 225-231.

Research output: Contribution to journalArticle

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