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Crosby, M.B.; Zhang, J.; Nowling, T.M.; Svenson, J.L.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
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Title |
Inflammatory modulation of PPAR gamma expression and activity |
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Journal Article |
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Year |
2006 |
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Clinical immunology |
Abbreviated Journal |
Clin Immunol |
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Volume  |
118 |
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2-3 |
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276-283 |
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Age Factors; Animals; Cell Line, Transformed; Cells, Cultured; Female; Inflammation Mediators/*physiology; Kidney/metabolism; Mesangial Cells/metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Mice, Knockout; Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type II/biosynthesis/genetics; PPAR gamma/*biosynthesis/*genetics/metabolism; Up-Regulation/immunology |
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Nitric oxide (NO) production increases with age in the lupus-prone MRL/lpr mouse, paralleling disease activity. One mechanism for excess NO production in MRL/lpr mice may be a defect in down-regulatory mechanisms of the iNOS pathway. A potential modulator of NO is the nuclear hormone receptor peroxisome proliferation activated receptor gamma (PPARgamma). We demonstrate that renal PPARgamma protein expression was altered as disease progressed in MRL/lpr mice, which paralleled increased iNOS protein expression. Additionally, MRL/lpr-derived primary mesangial cells expressed less PPARgamma than BALB/c mesangial cells and produced more NO in response to LPS and IFNgamma. Furthermore, PPARgamma activity was reduced in mesangial cells following exposure to inflammatory mediators. This activity was restored with the addition of a NOS enzyme inhibitor. These results indicate that the activation of inflammatory pathways may lead to reduced activity and expression of PPARgamma, further exacerbating the disease state. |
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Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA |
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1521-6616 |
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PMID:16303334 |
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refbase @ user @ |
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67 |
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Nicol, C.J. |
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Title |
How animals learn from each other |
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Journal Article |
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Year |
2006 |
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Applied Animal Behaviour Science |
Abbreviated Journal |
Appl. Anim. Behav. Sci. |
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100 |
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1-2 |
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58-63 |
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Social learning; Chickens; Demonstrators; Dominance |
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This paper explores ways by which animals may learn from one another, using examples drawn mostly from the chicken, an animal for which social learning is likely to be less dangerous than individual learning. In early life, the behaviour of the hen is important in encouraging chicks to peck at edible items. Maternal display not only attracts chicks to profitable food items, but also redirects their attention away from harmful or non-profitable items. Older chicks can enhance their foraging success by observing the behaviour of conspecifics within their own social group. Hens have been trained to perform a novel behaviour (key-pecking for food) by observation of a trained demonstrator bird. Moreover, observers learnt most from watching dominant demonstrators. Thus the ability to learn from others is not `fixed', but depends on the context and the social identity of both the observer and the demonstrator. |
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564 |
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Nicol, C.J.; Badnell-Waters, A.J.; Bice, R.; Kelland, A.; Wilson, A.D.; Harris, P.A. |
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The effects of diet and weaning method on the behaviour of young horses |
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Journal Article |
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2005 |
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Applied Animal Behaviour Science |
Abbreviated Journal |
Appl. Anim. Behav. Sci. |
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95 |
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3-4 |
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205-221 |
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Horse; Diet; Weaning; Temperament test |
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The effects of diet on horse behaviour have not previously been quantified in detail. In this study, we examined the behaviour of 17 foals from the age of 2 to 40 weeks. Each foal received either a starch and sugar (SS) diet or a fat and fibre (FF) diet. The two diets contained similar digestible energy, crude protein and micronutrients, but differed in the fat and non-structural carbohydrate balance. The baseline behaviour of the foals was observed every 2 weeks by focal animal sampling. Additional behavioural observations were conducted when the foals were weaned by one of two methods. Approximately 2 months after weaning, the temperament and tractability of the young horses was assessed using standardised tests. Responses to a novel object, to a novel person, and during a handling test were observed and quantified. Horses grew well on both diets with no apparent effects of diet on growth rate or baseline behaviour. Immediately after weaning, horses receiving the FF diet cantered less frequently (F = 5.10; p < 0.05), for a shorter duration (F = 7.23; p < 0.05) and appeared to be more settled. Foals that were barn-weaned appeared more stressed than foals that were paddock-weaned. In the temperament tests, horses receiving the FF diet spent significantly more time investigating (F = 6.78; p < 0.05), and less time looking at (F = 7.93; p < 0.05), the novel object than horses receiving the SS diet. They also spent less time walking away from the novel person (F = 5.16; p < 0.05) and their time taken to complete the handling test was significantly lower (F = 8.72; p = 0.01). Overall, the horses that received the FF diet appeared less distressed immediately after weaning and seemed calmer and more inquisitive during a range of temperament tests. |
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Equine Behaviour @ team @ |
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3642 |
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Cozzi, A.; Sighieri, C.; Gazzano, A.; Nicol, C.J.; Baragli, P. |
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Title |
Post-conflict friendly reunion in a permanent group of horses (Equus caballus) |
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2010 |
Publication |
Behavioural Processes |
Abbreviated Journal |
Behav. Process. |
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85 |
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2 |
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185-190 |
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aggression; affiliative interactions; conflict resolution; horse; post conflict; behaviour; reconciliation |
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Gregarious animals living in permanent social groups experience intra-group competition. Conflicts over resources can escalate into costly aggression and, in some conditions, non-dispersive forms of conflict resolution may be favoured. Post-conflict friendly reunions, hence reconciliation, have been described in a variety of species. The aim of this study was to explore, for the first time, the occurrence of reconciliation in a group of domestic horses (Equus caballus) and learn more about strategies used to maintain group cohesion. The behaviour of seven horses living as permanent group in an enclosure for at least 2 years was observed by video for 108 h from June to August 2007. We used a Post-Conflict/Matched Control method to assess the existence of reconciliation and third-party affiliation. Behaviours recorded Post-Conflict, or during Matched Control periods, were classified as affiliative based on previous descriptions of visual communication patterns in horses. The proportion of attracted pairs over total post-conflict situations was significantly greater than the proportion of dispersed pairs, both during dyadic interactions (p < 0.001) and during triadic interactions (p = 0.002). The results of the present study show that both dyadic reconciliation and third-party post-conflict affiliative interactions form important social mechanisms for managing post-conflict situations in horses. |
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0376-6357 |
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Equine Behaviour @ team @ |
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5168 |
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Guo, G.L.; Moffit, J.S.; Nicol, C.J.; Ward, J.M.; Aleksunes, L.A.; Slitt, A.L.; Kliewer, S.A.; Manautou, J.E.; Gonzalez, F.J. |
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Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
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Journal Article |
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2004 |
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Toxicological sciences : an official journal of the Society of Toxicology |
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Toxicol Sci |
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82 |
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2 |
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374-380 |
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Acetaminophen/pharmacokinetics/*toxicity; Analgesics, Non-Narcotic/pharmacokinetics/*toxicity; Animals; Aryl Hydrocarbon Hydroxylases/biosynthesis; Biotransformation; Blotting, Northern; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Membrane Proteins; Mice; Mice, Knockout; Oxidoreductases, N-Demethylating/biosynthesis; Pregnenolone Carbonitrile/pharmacology; Receptors, Cytoplasmic and Nuclear/*drug effects; Receptors, Steroid/*drug effects; Sulfhydryl Compounds/metabolism |
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The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation. |
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Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA |
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1096-6080 |
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PMID:15456926 |
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refbase @ user @ |
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71 |
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Nicol, C. J. |
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Equine learning: progress and suggestions for future research |
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Journal Article |
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2002 |
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Applied Animal Behaviour Science |
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Appl. Anim. Behav. Sci. |
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78 |
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2-4 |
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193-208 |
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Learning; Horse; Equine; Discrimination; Training |
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Horses are well able to form classical and instrumental associations and so the focus of much recent research has been on the stimulus control of instrumental learning. Horses appear to discriminate using spatial cues more easily than other stimulus features, as indicated both by the speed of initial task acquisition and by the extent to which acquired discriminations can be reversed. Phenomena associated with discrimination learning in laboratory animals, including generalisation and peak shift, have been demonstrated in horses. However, the ability of horses to classify stimuli into categories is more controversial. Although there is some evidence that horses may be able to form categories based on similarities in the physical appearance of different stimuli, there is currently no evidence that they are able to develop abstract concepts. Their performance on social learning tasks has also been poor. Few correlations are observed between the learning ability of individual horses on different tasks, suggesting that it may not be possible to classify individual horses as `good' or `poor' learners. Better learning performance by horses that are naturally calm is probably due to reduced interference in the learning process. Correct handling procedures can lower reactivity levels in horses, and may facilitate learning in some circumstances. Future research on equine learning needs to take into account the complex nature of equine social interaction. Studies on the effects of stress on learning, and on social and spatial cognition, are also particularly needed. |
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refbase @ user @ |
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405 |
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Hothersall, B.; Nicol, C. |
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Equine learning behaviour: accounting for ecological constraints and relationships with humans in experimental design |
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2007 |
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Behavioural Processes |
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Behav. Process. |
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76 |
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1 |
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45-48 |
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632 |
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Abeyesinghe, S.M.; Nicol, C.J.; Hartnell, S.J.; Wathes, C.M. |
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Can domestic fowl, Gallus gallus domesticus, show self-control? |
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Journal Article |
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2005 |
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Animal Behaviour. |
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Anim. Behav. |
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70 |
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1-11 |
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An important aspect of cognition is whether animals live exclusively in the present or can anticipate the future. Defined as self-control, the ability to choose a large, remote reinforcer over a small, proximate reinforcer available at the same frequency has been examined in a number of species, often proving difficult to demonstrate. We investigated self-control for food in domestic fowl using a standard two-key operant task and an equivalent two-choice return maze (TCRM) task. When hens chose between a 2-s delay to a 3-s feed access (impulsive) and a 6-s delay to a 7-s feed access (self-control), they appeared unable to discriminate in the TCRM but were impulsive in the operant task. We explored reasons for not choosing self-control in the operant task, first by examining the relation between feed access time and actual feed intake. A second operant experiment examined whether failure to show self-control could be attributed to an inability to combine the delay and access (quantity) reward information associated with choices to reach overall predictions of value. New hens chose between a 2-s delay to a 3-s feed access (impulsive) and either a 22-s delay to a 22-s feed access (standard self-control) or a 6-s delay to a 22-s feed access (jackpot self-control). While hens were impulsive in the standard condition, they showed significant and pronounced self-control in the jackpot condition, eliminating the possibility of an absolute cognitive constraint. Impulsive behaviour can instead be explained by temporal discounting: perceived depreciation of reward value as a function of the uncertainty associated with delay. Implications for welfare are discussed. |
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Equine Behaviour @ team @ |
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2897 |
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Nicol, C.J.; Badnell-Waters, A.J. |
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Suckling behaviour in domestic foals and the development of abnormal oral behaviour |
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Journal Article |
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2005 |
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Animal Behaviour. |
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Anim. Behav. |
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70 |
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1 |
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21-29 |
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We investigated how the behaviour of domestic foals, Equus caballus, living at pasture with their dams was associated with foal gender, mare rank and the development of abnormal oral behaviour, both during the preweaning period, and over a period of up to 4 years postweaning. A population of 186 foals belonging to private owners and commercial studs was studied. The behaviour of male and female foals hardly differed, but mare rank affected patterns of foal social interaction and suckling behaviour, with foals of subordinate mares involved in more affiliative interactions. These foals also spent more time in perisuckling activities such as teat nuzzling than foals of other mares. During the study, 18 foals developed abnormal oral behaviour before weaning and 42 foals developed abnormal oral behaviour after weaning. The development of abnormal oral behaviour was associated with suckling behaviour in a variety of ways. Foals that had already developed abnormal oral behaviour at the time of the preweaning observations were involved in more suckling terminations within bouts than normal foals or foals that developed future abnormal behaviour, and pushing the udder with the muzzle was most frequent in these foals. Foals that had no current abnormal oral behaviour, but that would develop this in the future, spent more time suckling and twice as much time teat nuzzling as other foals. The results add to the growing evidence of associations between digestive function and abnormal oral behaviour in horses. |
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Equine Behaviour @ team @ |
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3631 |
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Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. |
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Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha |
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Journal Article |
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2004 |
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Cancer research |
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Cancer Res |
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64 |
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11 |
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3849-3854 |
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Animals; Anticholesteremic Agents/pharmacology; Carcinogens/pharmacology; Cell Division; DNA Replication/drug effects; Fatty Acids/metabolism; Hepatocytes/cytology/drug effects/metabolism/*physiology; Humans; Mice; Mice, Transgenic; Oxidation-Reduction; Peroxisome Proliferators/pharmacology; Pyrimidines/pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Species Specificity; Transcription Factors/genetics/*physiology |
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Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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0008-5472 |
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PMID:15172993 |
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refbase @ user @ |
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