The peroxisome proliferator-activated receptor ␥ (PPAR␥) is a key regulator of terminal adipocyte differentiation. PPAR␦ is expressed in preadipocytes, but the importance of this PPAR subtype in adipogenesis has been a matter of debate. Here we present a critical evaluation of the role of PPAR␦ in adipocyte differentiation. We demonstrate that treatment of NIH-3T3 fibroblasts overexpressing PPAR␦ with standard adipogenic inducers led to induction of PPAR␥2 expression and terminal adipocyte differentiation in a manner that was strictly dependent on simultaneous administration of a PPAR␦ ligand and methylisobutylxanthine (MIX) or other cAMP elevating agents. We further show that ligands and MIX synergistically stimulated PPAR␦-mediated transactivation. In 3T3-L1 preadipocytes, simultaneous administration of a PPAR␦-selective ligand and MIX significantly enhanced the early expression of PPAR␥ and ALBP/aP2, but only modestly promoted terminal differentiation as determined by lipid accumulation. Finally, we provide evidence that synergistic activation of PPAR␦ promotes mitotic clonal expansion in 3T3-L1 cells with or without forced expression of PPAR␦. In conclusion, our results suggest that PPAR␦ may play a role in the proliferation of adipocyte precursor cells, whereas activation of endogenous PPAR␦ in 3T3-L1 cells appears to have only minor impact on the processes leading to terminal adipocyte differentiation.Adipocyte differentiation proceeds in a cascade-like manner by the sequential action of different classes of transcriptional regulators among which members of the CCAAT/enhancerbinding protein (C/EBP) 1 and the peroxisome proliferator-activated receptor (PPAR) families play crucial roles, and in a complex interdependent manner regulate clonal expansion, withdrawal from the cell cycle, and terminal differentiation (reviewed in Refs. 1-4). The PPAR family belongs to the superfamily of nuclear hormone receptors and comprises three subtypes, PPAR␣, PPAR␦ (also designated PPAR, FAAR, or NUC-1) and PPAR␥, the latter of which exists in two isoforms (5-8). The PPARs are ligand-activated transcription factors that bind as heterodimers with members of the retinoid X receptor (RXR) subfamily to PPAR response elements (PPREs) in the promoters/ enhancers of responsive genes. The PPARs are activated by a large variety of fatty acids and fatty acid metabolites, and direct binding of many of these activators to PPARs has been demonstrated (9 -12). Synthetic thiazolidinedione insulin-sensitizing antidiabetic drugs have been shown to be high affinity PPAR␥ ligands (13), and selective PPAR␦ ligands have recently been described (14 -16). Apart from ligands, the transactivation potential of PPAR␥ and PPAR␣ is regulated by phosphorylation (17-23) and by interaction with different families of coactivators and corepressors (24,25), and interaction with ligands and cofactors may in part be controlled by phosphorylation (26, 27).Activators of PPAR␥ promote adipocyte differentiation of preadipocytes and multipotent C3H10T 1/2 cells (1...
Research results that have been reported indicate that the specific outcomes of teamwork vary and are in part context-dependant, while less is known about the interaction between teamwork and psychological factors. This paper reviews research results published in scientific journals in the period 2000 Á/2005, and assesses current knowledge of teams and associated psychological factors. Furthermore, the review process identified the importance of team constituent factors (interdependence and team autonomy), team type and team size, and contextual factors for the results that were reported, and assessed the design and research-methodological foundations of those results. The main inclusion criteria for papers were that they had been based on field studies of formally established teams and were published in peer-reviewed scientific journals. Furthermore they must have been based on the use of questionnaires, and the occupational sector must have been identified. Fifty-five papers were identified for inclusion in the review. An almost consistent pattern of positive associations between psychological variables and teamwork was found to be reported across team types, team sizes, and contextual factors. Furthermore, the reported psychological factors appear to be positively linked to team autonomy and team interdependence. This paper discusses the strength of the interactions between teamwork and various psychological variables, and suggests directions for future research.
The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in fatty acid metabolism and energy homeostasis. The PPARs also play crucial roles in the control of cellular growth and differentiation. Especially, the recently emerged concept of ligand-dependent PPARgamma-mediated inhibition of cancer cell proliferation through induction of G(1)-phase arrest and differentiation is of clinical interest to cancer therapy. Tetradecylthioacetic acid (TTA) is a sulphur-substituted saturated fatty acid analog with unique biochemical properties. In this study, we investigated the effects of TTA-administration on cell proliferation in glioma cancer models. The rat glioma cell line BT4Cn, whether grown in culture or implanted in rats, expressed significant levels of PPARgamma and PPARdelta, with PPARgamma being the predominant PPAR subtype. In BT4Cn cells, TTA activated all PPAR subtypes in a dose-dependent manner. In cell culture experiments, the PPARgamma-selective ligand BRL49653 moderately inhibited growth of BT4Cn cells, whereas administration of TTA resulted in a marked growth inhibition. Administration of the PPARgamma-selective antagonist GW9662 abolished BRL49653-induced growth inhibition, but only marginally reduced the effect of TTA. TTA reduced tumor growth and increased the survival time of rats with implanted BT4Cn tumor. TTA-induced apoptosis in BT4Cn cells, and the administration of TTA led to cytochrome c release from mitochondria and increased the glutathione content in glioma cells. In conclusion, our results indicate that TTA inhibits proliferation of glioma cancer cells through both PPARgamma-dependent and PPARgamma-independent pathways, of which the latter appears to predominate.
Regulatory agencies often delegate responsibility for implementing policy to agencies at lower levels of government. This article models strategic bargaining between New York State regulatory principals at the Department of Environmental Conservation (DEC) and county landfill agents as an iterated prisoner’s dilemma game. Data are drawn from regional DEC and county records over a 7-year period. Local regulatory agents balance local political pressures, career aspirations, and the probability of being caught and punished in deciding whether to cooperate or defect with regional DEC regulators. Regional DEC regulatory principals balance their support from governor and legislature, the importance of the regulatory issue, and the constraints of scarce resources in deciding whether to cooperate or defect with local landfill operators.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.