scholarly journals Lysophosphatidic acid attenuates the cytotoxic effects and degree of peroxisome proliferator-activated receptor γ activation induced by 15-deoxyΔ12,14-prostaglandin J2 in neuroblastoma cells

2004 ◽  
Vol 382 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Helen A. RODWAY ◽  
Alan N. HUNT ◽  
Janice A. KOHLER ◽  
Anthony D. POSTLE ◽  
Karen A. LILLYCROP
Keyword(s):  
Cell Death ◽  
Growth Inhibition ◽  
Lysophosphatidic Acid ◽  
Serum Lipid ◽  
Neuroblastoma Cells ◽  
Cellular Responses ◽  
Complete Medium ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Phosphoinositide 3 Kinase

PPARγ (peroxisome proliferator-activated receptor γ) is a ligand-activated transcription factor that responds to 15dPGJ2 (15-deoxy-Δ12,14-prostglandin J2). 15dPGJ2, in vitro, halts neuroblastoma cell growth, but reported mechanisms vary. Here we evaluated the modulatory effects of endogenous serum lipid mitogens upon the extent of 15dPGJ2-induced growth inhibition and on the precise cellular responses of neuroblastoma cells to PPARγ activation. We show that 15dPGJ2 specifically inhibited cell growth in both complete and delipidated media. 15dPGJ2-induced growth inhibition was accompanied by decreased cell viability, although the effect was far more marked in delipidated medium than in complete medium. Incubation with 15dPGJ2 in complete medium resulted in cytoplasmic changes characteristic of type II programmed cell death (autophagy), while prior serum lipid removal resulted in cell death via an apoptotic mechanism. These distinct, serum lipid-dependent cellular responses to 15dPGJ2 were accompanied by increases in the expression of a reporter gene construct containing a PPAR response element of 2.3-fold in complete medium, but of 4.8-fold in delipidated medium. Restoration of the serum lysolipid LPA (lysophosphatidic acid) to cells in delipidated medium reduced 15dPGJ2-mediated PPARγ activation, growth inhibition and cell death; following addition of S1P (sphingosine 1-phosphate), decreases were apparent but more marginal. Further, while the effects of LPA in delipidated medium were mediated through a Gi/phosphoinositide 3-kinase/MAPK (mitogen-activated protein kinase) pathway, those of S1P did not involve the MAPK component. These data suggest that the serum lysolipid LPA modulates the degree of PPARγ activation and the precise cellular response to 15dPGJ2 via activation of a Gi/phosphoinositide 3-kinase/MAPK pathway.

Expression of Peroxisome Proliferator-Activated Receptor γ in Renal Cell Carcinoma and Growth Inhibition by Its Agonists

2001 ◽  
Vol 287 (3) ◽  
pp. 727-732 ◽  
Author(s):  
Ken-ichiro Inoue ◽  
Yutaka Kawahito ◽  
Yasunori Tsubouchi ◽  
Masataka Kohno ◽  
Rikio Yoshimura ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Growth Inhibition ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Peroxisome-proliferator-activated receptor-binding protein (PBP) is essential for the growth of active Notch4-immortalized mammary epithelial cells by activating SOX10 expression

2009 ◽  
Vol 425 (2) ◽  
pp. 435-444 ◽  
Author(s):  
Yiwei Tony Zhu ◽  
Yuzhi Jia ◽  
Liping Hu ◽  
Chao Qi ◽  
Megana K. Prasad ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Receptor Binding ◽  
Binding Protein ◽  
Active Form ◽  
Mammary Epithelial ◽  
Peroxisome Proliferator ◽  
Mammary Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sox10 Expression ◽  
Receptor Binding Protein

PBP (peroxisome-proliferator-activated receptor-binding protein) [Med1 (mediator 1)/TRAP220 (thyroid-hormone-receptor-associated protein 220)] is essential for mammary gland development. We established a mammary epithelial cell line with a genotype of PBPLoxP/LoxP by expressing an active form of Notch4. Null mutation of PBP caused severe growth inhibition of the Notch4-immortalized mammary cells. We found that truncated PBP without the two LXXLL motifs could reverse the growth inhibition due to the deficiency of endogenous PBP, indicating that signalling through nuclear receptors is unlikely to be responsible for the growth inhibition as the result of PBP deficiency. Loss of PBP expression was shown to completely ablate the expression of SOX10 [Sry-related HMG (high-mobility group) box gene 10]. The re-expression of SOX10 was capable of reversing the growth inhibition due to PBP deficiency, whereas suppressed expression of SOX10 inhibited the growth of Notch4-immortalized mammary cells. Further studies revealed PBP is directly recruited to the enhancer of the SOX10 gene, indicating that SOX10 is a direct target gene of PBP. We conclude that PBP is essential for the growth of Notch4-immortalized mammary cells by activating SOX10 expression, providing a potential molecular mechanism through which PBP regulates the growth of mammary stem/progenitor cells.

scholarly journals Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18932 ◽  
Author(s):  
Cliona M. Stapleton ◽  
Douglas G. Mashek ◽  
Shuli Wang ◽  
Cynthia A. Nagle ◽  
Gary W. Cline ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Cho Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals PPAR-γ Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shiyan Peng ◽  
Junmei Xu ◽  
Wei Ruan ◽  
Suobei Li ◽  
Feng Xiao
Keyword(s):  
Cell Death ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Cardiac Inflammation ◽  
Ppar Γ

Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis. Rats were subjected to cecal ligation and puncture (CLP) with or without PPAR-γ agonist (rosiglitazone) or antagonist T0070907 (T007). After CLP, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated proinflammatory cytokines, and increased apoptosis, necrosis, and necroptosis. This process is corresponded with decreased inhibitor κB (IκBα) and increased NF-κB, receptor-interacting protein kinase-1 (RIP1), RIP3, and mixed lineage kinase-like (MLKL) protein. Activation of PPAR-γ by rosiglitazone pretreatment enhanced PPAR-γ activity and prevented these changes, thereby improving the survival of septic rats. In contrast, inhibition of PPAR-γ by T007 further exacerbated the condition, dropping the survival rate to nearly 0%. In conclusion, PPAR-γ activation by reducing proinflammatory cytokines, apoptosis, and necroptosis in the myocardium prevents septic myocardial dysfunction.

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