Peroxisome proliferator-activated receptor γ promotes lymphocyte survival through its actions on cellular metabolic activities

Seung Hee Jo, Chunyan Yang, Qi Miao, Michal Marzec, Mariusz A. Wasik, Pin Lu, Y. Lynn Wang

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a metabolic regulator that plays an important role in sensitizing tissues to the action of insulin and in normalizing serum glucose and free fatty acids in type 2 diabetic patients. The receptor has also been implicated in the modulation of inflammatory responses, and ligands of PPARγ have been found to induce apoptosis in lymphocytes. However, apoptosis induction may not depend on the receptor, because high doses of PPARγ agonists are required for this process. Using cells containing or lacking PPARγ, we reported previously that PPARγ attenuates apoptosis induced by cytokine withdrawal in a murine lymphocytic cell line via a receptor-dependent mechanism. PPARγ exerts this effect by enhancing the ability of cells to maintain their mitochondrial membrane potential during cytokine deprivation. In this report, we demonstrate that activation of PPARγ also protects cells from serum starvation-induced apoptosis in human T lymphoma cell lines. Furthermore, we show that the survival effect of PPARγ is mediated through its actions on cellular metabolic activities. In cytokine-deprived cells, PPARγ attenuates the decline in ATP level and suppresses accumulation of reactive oxygen species (ROS). Moreover, PPARγ regulates ROS through its coordinated transcriptional control of proteins and enzymes involved in ROS scavenging, including uncoupling protein 2, catalase, and copper zinc superoxide dismutase. Our studies identify cell survival promotion as a novel activity of PPARγ and suggest that PPARγ may modulate cytokine withdrawal-induced activated T cell death.

Original languageEnglish
Pages (from-to)3737-3745
Number of pages9
JournalJournal of Immunology
Volume177
Issue number6
DOIs
StatePublished - Sep 15 2006

Keywords

  • Animals
  • Apoptosis/immunology
  • B-Lymphocyte Subsets/cytology
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival/immunology
  • Culture Media, Serum-Free
  • Cytokines/deficiency
  • Humans
  • Ligands
  • Lymphocyte Activation/immunology
  • Lymphocyte Subsets/cytology
  • Mice
  • PPAR gamma/metabolism
  • Stem Cells/cytology
  • T-Lymphocyte Subsets/cytology

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