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Michel Pierre - One of the best experts on this subject based on the ideXlab platform.
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map kinase cascades are activated in astrocytes and preadipocytes by 15 deoxy δ12 14 prostaglandin j2 and the thiazolidinedione ciglitazone through peroxisome proliferator activator receptor γ independent mechanisms involving reactive oxygenated spec
Journal of Biological Chemistry, 2002Co-Authors: Anne Marie Lennon, Martine Ramauge, Audrey Dessouroux, Michel PierreAbstract:Abstract 15-Deoxy-Δ12–14-prostaglandin J2 (dPGJ2) and Thiazolidinediones are known as ligands for the peroxisome proliferator activator receptor γ (PPARγ) a member of the nuclear receptor superfamily. Herein, we show that dPGJ2 activates, in cultured primary astrocytes, Erk, Jnk, p38 MAP kinase, and ASK1, a MAP kinase kinase kinase, which can be involved in the activation of Jnk and p38 MAP kinase. The activation kinetic is similar for the three MAP kinase. The activation of the MAP kinases is detectable around 0.5 h. The activation increases with dPGJ2 in a dose dependent manner (0–15 μm). A scavenger of reactive oxygenated species (ROS), N-acetylcysteine (NAC) at 20 mm, completely suppresses the activation of MAP kinases and ASK1, suggesting a role for oxidative stress in the activation mechanism. Other prostaglandin cyclopentenones than dPGJ2, A2, and to a lesser degree, A1 also stimulate the MAP kinases, although they do not bind to PPARγ. Ciglitazone (20 μm), a thiazolidinedione that mimics several effects of dPGJ2 in different cell types, also activates the three MAP kinase families and ASK1 in cultured astrocytes. However the activation is more rapid (it is detectable at 0.25 h) and more sustained (it is still strong after 4 h). NAC prevents the activation of the three MAP kinase families by ciglitazone. Another thiazolidinedione that binds to PPARγ, rosiglitazone, does not activate MAP kinases, indicating that the effect of ciglitazone on MAP kinases is independent of PPAR γ. Ciglitazone and less strongly dPGJ2 activate Erk in undifferentiated cells of the adipocyte cell line 1B8. Ciglitazone also activates Jnk and p38 MAP kinase in these preadipocytes. Our findings suggest that a part of the biological effects of dPGJ2 and ciglitazone involve the activation of the three MAP kinase families probably through PPARγ-independent mechanisms involving ROS.
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MAP Kinase Cascades Are Activated in Astrocytes and Preadipocytes by 15-Deoxy-Δ12–14-prostaglandin J2 and the Thiazolidinedione Ciglitazone through Peroxisome Proliferator Activator Receptor γ-independent Mechanisms Involving Reactive Oxygenated Spec
Journal of Biological Chemistry, 2002Co-Authors: Anne Marie Lennon, Martine Ramauge, Audrey Dessouroux, Michel PierreAbstract:Abstract 15-Deoxy-Δ12–14-prostaglandin J2 (dPGJ2) and Thiazolidinediones are known as ligands for the peroxisome proliferator activator receptor γ (PPARγ) a member of the nuclear receptor superfamily. Herein, we show that dPGJ2 activates, in cultured primary astrocytes, Erk, Jnk, p38 MAP kinase, and ASK1, a MAP kinase kinase kinase, which can be involved in the activation of Jnk and p38 MAP kinase. The activation kinetic is similar for the three MAP kinase. The activation of the MAP kinases is detectable around 0.5 h. The activation increases with dPGJ2 in a dose dependent manner (0–15 μm). A scavenger of reactive oxygenated species (ROS), N-acetylcysteine (NAC) at 20 mm, completely suppresses the activation of MAP kinases and ASK1, suggesting a role for oxidative stress in the activation mechanism. Other prostaglandin cyclopentenones than dPGJ2, A2, and to a lesser degree, A1 also stimulate the MAP kinases, although they do not bind to PPARγ. Ciglitazone (20 μm), a thiazolidinedione that mimics several effects of dPGJ2 in different cell types, also activates the three MAP kinase families and ASK1 in cultured astrocytes. However the activation is more rapid (it is detectable at 0.25 h) and more sustained (it is still strong after 4 h). NAC prevents the activation of the three MAP kinase families by ciglitazone. Another thiazolidinedione that binds to PPARγ, rosiglitazone, does not activate MAP kinases, indicating that the effect of ciglitazone on MAP kinases is independent of PPAR γ. Ciglitazone and less strongly dPGJ2 activate Erk in undifferentiated cells of the adipocyte cell line 1B8. Ciglitazone also activates Jnk and p38 MAP kinase in these preadipocytes. Our findings suggest that a part of the biological effects of dPGJ2 and ciglitazone involve the activation of the three MAP kinase families probably through PPARγ-independent mechanisms involving ROS.
Sandy Giuliano - One of the best experts on this subject based on the ideXlab platform.
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ciglitazone negatively regulates cxcl1 signaling through mitf to suppress melanoma growth
Cell Death & Differentiation, 2011Co-Authors: Yann Cheli, Tijana Tomic, Thomas Botton, Alexandre Puissant, Sandy GiulianoAbstract:We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPARγ activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the downregulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, whereas extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results show that anti-melanoma effects of Thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.
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Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth
Cell Death and Differentiation, 2010Co-Authors: Thomas Botton, Yann Cheli, Tijana Tomic, Alexandre Puissant, Sandy Giuliano, Lluis Fajas, Marcel Deckert, Jean-paul Ortonne, Corine Bertololotto, Sophie Tartare-deckertAbstract:We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPAR activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the down regulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, while extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results demonstrate that anti-melanoma effects of Thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.
Thomas Botton - One of the best experts on this subject based on the ideXlab platform.
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ciglitazone negatively regulates cxcl1 signaling through mitf to suppress melanoma growth
Cell Death & Differentiation, 2011Co-Authors: Yann Cheli, Tijana Tomic, Thomas Botton, Alexandre Puissant, Sandy GiulianoAbstract:We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPARγ activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the downregulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, whereas extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results show that anti-melanoma effects of Thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.
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Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth
Cell Death and Differentiation, 2010Co-Authors: Thomas Botton, Yann Cheli, Tijana Tomic, Alexandre Puissant, Sandy Giuliano, Lluis Fajas, Marcel Deckert, Jean-paul Ortonne, Corine Bertololotto, Sophie Tartare-deckertAbstract:We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPAR activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the down regulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, while extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results demonstrate that anti-melanoma effects of Thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.
Ronald M Evans - One of the best experts on this subject based on the ideXlab platform.
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15 deoxy δ12 14 prostaglandin j2 is a ligand for the adipocyte determination factor pparγ
Cell, 1995Co-Authors: Barry M Forman, Peter Tontonoz, Jasmine Chen, Regina P Brun, Bruce M Spiegelman, Ronald M EvansAbstract:Abstract Regulation of adipose cell mass is a critical homeostatic process in higher vertebrates. The conversion of fibroblasts into cells of the adipose lineage is induced by expression of the orphan nuclear receptor PPARyγ. This suggests that an endogenous PPARγ ligand may be an important regulator of adipogenesis. By assaying arachidonate metabolites for their capacity to activate PPAR response elements, we have identified 15-deoxy- Δ 12,14 -prostaglandin J 2 as both a PPARγ ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPARγ and act as potent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic Thiazolidinediones initiate key transcriptional events through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPARγ and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders.
Anne Marie Lennon - One of the best experts on this subject based on the ideXlab platform.
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map kinase cascades are activated in astrocytes and preadipocytes by 15 deoxy δ12 14 prostaglandin j2 and the thiazolidinedione ciglitazone through peroxisome proliferator activator receptor γ independent mechanisms involving reactive oxygenated spec
Journal of Biological Chemistry, 2002Co-Authors: Anne Marie Lennon, Martine Ramauge, Audrey Dessouroux, Michel PierreAbstract:Abstract 15-Deoxy-Δ12–14-prostaglandin J2 (dPGJ2) and Thiazolidinediones are known as ligands for the peroxisome proliferator activator receptor γ (PPARγ) a member of the nuclear receptor superfamily. Herein, we show that dPGJ2 activates, in cultured primary astrocytes, Erk, Jnk, p38 MAP kinase, and ASK1, a MAP kinase kinase kinase, which can be involved in the activation of Jnk and p38 MAP kinase. The activation kinetic is similar for the three MAP kinase. The activation of the MAP kinases is detectable around 0.5 h. The activation increases with dPGJ2 in a dose dependent manner (0–15 μm). A scavenger of reactive oxygenated species (ROS), N-acetylcysteine (NAC) at 20 mm, completely suppresses the activation of MAP kinases and ASK1, suggesting a role for oxidative stress in the activation mechanism. Other prostaglandin cyclopentenones than dPGJ2, A2, and to a lesser degree, A1 also stimulate the MAP kinases, although they do not bind to PPARγ. Ciglitazone (20 μm), a thiazolidinedione that mimics several effects of dPGJ2 in different cell types, also activates the three MAP kinase families and ASK1 in cultured astrocytes. However the activation is more rapid (it is detectable at 0.25 h) and more sustained (it is still strong after 4 h). NAC prevents the activation of the three MAP kinase families by ciglitazone. Another thiazolidinedione that binds to PPARγ, rosiglitazone, does not activate MAP kinases, indicating that the effect of ciglitazone on MAP kinases is independent of PPAR γ. Ciglitazone and less strongly dPGJ2 activate Erk in undifferentiated cells of the adipocyte cell line 1B8. Ciglitazone also activates Jnk and p38 MAP kinase in these preadipocytes. Our findings suggest that a part of the biological effects of dPGJ2 and ciglitazone involve the activation of the three MAP kinase families probably through PPARγ-independent mechanisms involving ROS.
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MAP Kinase Cascades Are Activated in Astrocytes and Preadipocytes by 15-Deoxy-Δ12–14-prostaglandin J2 and the Thiazolidinedione Ciglitazone through Peroxisome Proliferator Activator Receptor γ-independent Mechanisms Involving Reactive Oxygenated Spec
Journal of Biological Chemistry, 2002Co-Authors: Anne Marie Lennon, Martine Ramauge, Audrey Dessouroux, Michel PierreAbstract:Abstract 15-Deoxy-Δ12–14-prostaglandin J2 (dPGJ2) and Thiazolidinediones are known as ligands for the peroxisome proliferator activator receptor γ (PPARγ) a member of the nuclear receptor superfamily. Herein, we show that dPGJ2 activates, in cultured primary astrocytes, Erk, Jnk, p38 MAP kinase, and ASK1, a MAP kinase kinase kinase, which can be involved in the activation of Jnk and p38 MAP kinase. The activation kinetic is similar for the three MAP kinase. The activation of the MAP kinases is detectable around 0.5 h. The activation increases with dPGJ2 in a dose dependent manner (0–15 μm). A scavenger of reactive oxygenated species (ROS), N-acetylcysteine (NAC) at 20 mm, completely suppresses the activation of MAP kinases and ASK1, suggesting a role for oxidative stress in the activation mechanism. Other prostaglandin cyclopentenones than dPGJ2, A2, and to a lesser degree, A1 also stimulate the MAP kinases, although they do not bind to PPARγ. Ciglitazone (20 μm), a thiazolidinedione that mimics several effects of dPGJ2 in different cell types, also activates the three MAP kinase families and ASK1 in cultured astrocytes. However the activation is more rapid (it is detectable at 0.25 h) and more sustained (it is still strong after 4 h). NAC prevents the activation of the three MAP kinase families by ciglitazone. Another thiazolidinedione that binds to PPARγ, rosiglitazone, does not activate MAP kinases, indicating that the effect of ciglitazone on MAP kinases is independent of PPAR γ. Ciglitazone and less strongly dPGJ2 activate Erk in undifferentiated cells of the adipocyte cell line 1B8. Ciglitazone also activates Jnk and p38 MAP kinase in these preadipocytes. Our findings suggest that a part of the biological effects of dPGJ2 and ciglitazone involve the activation of the three MAP kinase families probably through PPARγ-independent mechanisms involving ROS.
