TY - JOUR
T1 - Peroxisome proliferator-activated receptor γ promotes lymphocyte survival through its actions on cellular metabolic activities
AU - Jo, Seung Hee
AU - Yang, Chunyan
AU - Miao, Qi
AU - Marzec, Michal
AU - Wasik, Mariusz A.
AU - Lu, Pin
AU - Wang, Y. Lynn
PY - 2006/9/15
Y1 - 2006/9/15
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis/immunology
KW - B-Lymphocyte Subsets/cytology
KW - Cell Line
KW - Cell Line, Tumor
KW - Cell Survival/immunology
KW - Culture Media, Serum-Free
KW - Cytokines/deficiency
KW - Humans
KW - Ligands
KW - Lymphocyte Activation/immunology
KW - Lymphocyte Subsets/cytology
KW - Mice
KW - PPAR gamma/metabolism
KW - Stem Cells/cytology
KW - T-Lymphocyte Subsets/cytology
UR - http://www.scopus.com/inward/record.url?scp=33748477701&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000240475300027&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.4049/jimmunol.177.6.3737
DO - 10.4049/jimmunol.177.6.3737
M3 - Article
C2 - 16951334
SN - 0022-1767
VL - 177
SP - 3737
EP - 3745
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -