Multiple levels of regulation of selenoprotein biosynthesis revealed from the analysis of human glioma cell lines

David B. Mansur, Honglin Hao, Vadim N. Gladyshev, Konstantin V. Korotkov, Yajun Hu, Mohamed E. Moustafa, Muhammad A. El-Saadani, Bradley A. Carlson, Dolph L. Hatfield, Alan M. Diamond

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


To gain a better understanding of the biological consequences of the exposure of tumor cells to selenium, we evaluated the selenium-dependent responses of two selenoproteins (glutathione peroxidase and the recently characterized 15-kDa selenoprotein) in three human glioma cell lines. Protein levels, mRNA levels, and the relative distribution of the two selenocysteine tRNA isoacceptors (designated mcm5U and mcm5Um) were determined for standard as well as selenium-supplemented conditions. The human malignant glioma cell lines D54, U251, and U87 were maintained in normal or selenium-supplemented (30 nM sodium selenite) conditions. Northern blot analysis demonstrated only minor increases in steady-state GSHPx-1 mRNA in response to selenium addition. Baseline glutathione peroxidase activity was 10.7 ± 0.7, 7.6 ± 0.7, and 4.3 ± 0.7 nmol NADPH oxidized/min/mg protein for D54, U251, and U87, respectively, as determined by the standard coupled spectrophotometric assay. Glutathione peroxidase activity increased in a cell line-specific manner to 19.7 ± 1.4, 15.6 ± 2.1, and 6.7 ± 0.5 nmol NADPH oxidized/min/mg protein, respectively, as did a proportional increase in cellular resistance to H2O2, in response to added selenium. The 15-kDa selenoprotein mRNA levels likewise remained constant despite selenium supplementation. The selenium-dependent change in distribution between the two selenocysteine tRNA isoacceptors also occurred in a cell line-specific manner. The percentage of the methylated isoacceptor, mcm5Um, changed from 35.5 to 47.2 for D54, from 38.1 to 47.3 for U251, and from 49.0 to 47.6 for U87. These data represent the first time that selenium-dependent changes in selenoprotein mRNA and protein levels, as well as selenocysteine tRNA distribution, were examined in human glioma cell lines. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)489-497
Number of pages9
JournalBiochemical Pharmacology
Issue number4
StatePublished - Aug 15 2000

Bibliographical note

Funding Information:
The authors wish to express their appreciation to G. Murillo for her assistance with the statistical analysis of the data presented. This work was supported by Grant R01 CA81153 to A.M.D., and a Cancer Research Foundation of America grant to V.N.G.


  • Glioma
  • Glutathione peroxidase
  • Selenium
  • Selenocysteine
  • Selenoprotein
  • tRNA

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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