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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes

I Wu1, S C Shin, Y Cao

  • 1Division of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Cell Death & Disease
|January 11, 2013
PubMed

Insights

Glucocorticoid receptor (GR) isoforms selectively induce T-cell apoptosis, contributing to anti-inflammatory effects. Understanding these GR isoform functions may lead to improved glucocorticoid therapies.

Area of Science:

  • Molecular biology
  • Immunology
  • Cell biology

Background:

  • Glucocorticoids (GCs) exert anti-inflammatory and antineoplastic effects partly through T-cell apoptosis.
  • Glucocorticoid receptor (GR) translational isoforms possess distinct proapoptotic activities, as observed in osteosarcoma cells.

Purpose of the Study:

  • To investigate whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells.
  • To identify genes and pathways involved in GR isoform-mediated apoptosis in T-cells.

Main Methods:

  • Generation of Jurkat T-cell lines stably expressing individual GR isoforms.
  • Treatment with dexamethasone (DEX) and assessment of apoptosis.
  • cDNA microarray analysis to compare gene expression profiles.
  • Chromatin immunoprecipitation assays to investigate GR isoform functions.

Main Results:

  • Dexamethasone (DEX) induced apoptosis in Jurkat cells expressing GR-A, -B, or -C isoforms, but not GR-D.
  • Distinct proapoptotic transcriptomes were identified in DEX-sensitive (GR-C3) versus insensitive (GR-D3) cells.
  • Genes directly involved in apoptosis and cell killing were regulated by proapoptotic GR-C3 but not GR-D3.
  • All GR isoforms suppressed mitogen-stimulated cytokines, while GR-C isoforms were upregulated in activated T cells.

Conclusions:

  • GR isoforms exhibit selective proapoptotic functions in T-cells, mediated by distinct transcriptomes and chromatin modification abilities.
  • The differential expression and function of GR isoforms contribute to the tissue- and individual-selective actions of glucocorticoids.
  • These findings provide a basis for developing improved glucocorticoid therapeutics targeting specific GR isoforms.

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