Peroxisome Proliferator-Activated Receptor γ Promotes Lymphocyte Survival through Its Actions on Cellular Metabolic Activities.

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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 contg. or lacking PPARγ, the authors 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, the authors demonstrate that activation of PPARγ also protects cells from serum starvation-induced apoptosis in human T lymphoma cell lines. Furthermore, the authors 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. The authors' studies identify cell survival promotion as a novel activity of PPARγ and suggest that PPARγ may modulate cytokine withdrawal-induced activated T cell death. [on SciFinder(R)]
Original languageEnglish
JournalJournal of Immunology
Issue number6
Pages (from-to)3737-3745
Number of pages9
Publication statusPublished - 2006
Externally publishedYes

Bibliographical note

M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.

CAPLUS AN 2006:937308(Journal)

    Research areas

  • PPARgamma lymphocyte apoptosis metab oxygen

ID: 202375606