Records |
Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
Keywords |
9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers |
Abstract |
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. |
Address |
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0143-3334 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:15073042 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
76 |
Permanent link to this record |
|
|
|
Author |
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. |
Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
Journal Article |
Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
Volume |
82 |
Issue |
2 |
Pages |
374-380 |
Keywords |
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 |
Abstract |
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. |
Address |
Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
1096-6080 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:15456926 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
71 |
Permanent link to this record |
|
|
|
Author |
Boray, J.C. |
Title |
Experimental fascioliasis in Australia |
Type |
Journal Article |
Year |
1969 |
Publication |
Advances in Parasitology |
Abbreviated Journal |
Adv Parasitol |
Volume |
7 |
Issue |
|
Pages |
95-210 |
Keywords |
Adaptation, Biological; Adaptation, Physiological; Animal Nutrition Physiology; Animals; Animals, Laboratory; Australia; Cattle; *Cattle Diseases/pathology; Climate; *Disease Vectors; Ecology; Electron Transport; Estivation; Fasciola hepatica/enzymology/*growth & development/metabolism/physiology; Fascioliasis/epidemiology/immunology/*prevention & control/veterinary; Glycolysis; Guinea Pigs; Horses; Humans; Larva/growth & development/physiology; Marsupialia; Metamorphosis, Biological; Mice; New Guinea; New Zealand; Parasite Egg Count; Rats; Seasons; Sheep; *Sheep Diseases/pathology |
Abstract |
|
Address |
|
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0065-308X |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:4935272 |
Approved |
no |
Call Number |
Equine Behaviour @ team @ |
Serial |
2744 |
Permanent link to this record |
|
|
|
Author |
Jeong, S.; Han, M.; Lee, H.; Kim, M.; Kim, J.; Nicol, C.J.; Kim, B.H.; Choi, J.H.; Nam, K.-H.; Oh, G.T.; Yoon, M. |
Title |
Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice |
Type |
Journal Article |
Year |
2004 |
Publication |
Metabolism: clinical and experimental |
Abbreviated Journal |
Metabolism |
Volume |
53 |
Issue |
10 |
Pages |
1284-1289 |
Keywords |
Adipose Tissue/*anatomy & histology/drug effects; Animals; Antilipemic Agents/*pharmacology; Body Composition/*drug effects; Body Weight/drug effects; Dietary Fats/*pharmacology; Eating/drug effects; Fatty Acids/metabolism; Female; Gene Expression Regulation/drug effects; Leptin/metabolism; Liver/metabolism; Mice; Mice, Inbred C57BL; Ovariectomy; Procetofen/*pharmacology; RNA, Messenger/biosynthesis/genetics; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism; Transcription Factors/biosynthesis/genetics/metabolism; Weight Gain/*drug effects |
Abstract |
Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice. |
Address |
Department of Life Sciences, Mokwon University, Taejon, Korea |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0026-0495 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:15375783 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
72 |
Permanent link to this record |
|
|
|
Author |
Gavrilova, O.; Haluzik, M.; Matsusue, K.; Cutson, J.J.; Johnson, L.; Dietz, K.R.; Nicol, C.J.; Vinson, C.; Gonzalez, F.J.; Reitman, M.L. |
Title |
Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass |
Type |
Journal Article |
Year |
2003 |
Publication |
The Journal of biological chemistry |
Abbreviated Journal |
J Biol Chem |
Volume |
278 |
Issue |
36 |
Pages |
34268-34276 |
Keywords |
Adipose Tissue/*metabolism; Animals; Blotting, Southern; Blotting, Western; Female; Hypoglycemia/genetics; Insulin Resistance/genetics; Lipid Metabolism; Liver/*metabolism; Liver Diseases/genetics/*metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; RNA/metabolism; Receptors, Cytoplasmic and Nuclear/*genetics/*physiology; Recombination, Genetic; Thiazoles/pharmacology; *Thiazolidinediones; Time Factors; Transcription Factors/*genetics/*physiology; Triglycerides/*metabolism |
Abstract |
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that mediates the antidiabetic effects of thiazolidinediones. PPAR gamma is present in adipose tissue and becomes elevated in fatty livers, but the roles of specific tissues in thiazolidinedione actions are unclear. We studied the function of liver PPAR gamma in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type mice. In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance. Inactivation of AZIP liver PPAR gamma also abolished the hypoglycemic and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of adipose tissue, the liver is a primary and major site of thiazolidinedione action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice lacking liver PPAR gamma, suggesting that adipose tissue is the major site of thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice without liver PPAR gamma, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus, liver PPAR gamma regulates triglyceride homeostasis, contributing to hepatic steatosis, but protecting other tissues from triglyceride accumulation and insulin resistance. |
Address |
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. oksanag@bdg10.niddk.nih.gov |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0021-9258 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:12805374 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
81 |
Permanent link to this record |
|
|
|
Author |
Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. |
Title |
PPARgamma in endothelial cells influences high fat diet-induced hypertension |
Type |
Journal Article |
Year |
2005 |
Publication |
American journal of hypertension : journal of the American Society of Hypertension |
Abbreviated Journal |
Am J Hypertens |
Volume |
18 |
Issue |
4 Pt 1 |
Pages |
549-556 |
Keywords |
Administration, Oral; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Diabetes Mellitus, Type 2/physiopathology; Dietary Fats/*administration & dosage/pharmacology; Dose-Response Relationship, Drug; Endothelial Cells/*metabolism; Female; Heart Rate/drug effects; Hypertension/*etiology; Ligands; Male; Mice; Mice, Knockout; PPAR gamma/*metabolism; Sodium Chloride/administration & dosage/pharmacology; Thiazolidinediones/pharmacology |
Abstract |
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful. |
Address |
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0895-7061 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:15831367 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
69 |
Permanent link to this record |
|
|
|
Author |
Menges, R.W.; Furcolow, M.L.; Selby, L.A.; Habermann, R.T.; Smith, C.D. |
Title |
Ecologic studies of histoplasmosis |
Type |
Journal Article |
Year |
1967 |
Publication |
American Journal of Epidemiology |
Abbreviated Journal |
Am J Epidemiol |
Volume |
85 |
Issue |
1 |
Pages |
108-119 |
Keywords |
Adolescent; Adult; Animals; Antibodies/*analysis; Carnivora; Cats; Cattle; Child; Child, Preschool; Dogs; Ecology; Female; Fluorescent Antibody Technique; Histoplasma/isolation & purification; Histoplasmin; Histoplasmosis/*epidemiology/*immunology; Horses; Humans; Infant; Infant, Newborn; Kansas; Male; Marsupialia; Mice; Middle Aged; Missouri; Rabbits; Skin Tests; *Soil Microbiology; Swine |
Abstract |
|
Address |
|
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0002-9262 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:5334640 |
Approved |
no |
Call Number |
Equine Behaviour @ team @ |
Serial |
2747 |
Permanent link to this record |
|
|
|
Author |
Yamada, T.; Rojanasuphot, S.; Takagi, M.; Wungkobkiat, S.; Hirota, T. |
Title |
Studies on an epidemic of Japanese encephalitis in the northern region of Thailand in 1969 and 1970 |
Type |
Journal Article |
Year |
1971 |
Publication |
Biken Journal |
Abbreviated Journal |
Biken J |
Volume |
14 |
Issue |
3 |
Pages |
267-296 |
Keywords |
Adolescent; Adult; Animals; Arboviruses/immunology; Buffaloes; Cattle; Chickens; Child; Child, Preschool; Cross Reactions; Culicidae; Dengue Virus/immunology; Disease Outbreaks; Ducks; Ecology; Encephalitis Virus, Japanese/immunology/isolation & purification; Encephalitis, Japanese/cerebrospinal fluid/*epidemiology/immunology/microbiology/mortality; Female; Hemagglutination Inhibition Tests; Hemorrhagic Fevers, Viral/epidemiology; Horses; Humans; Infant; Male; Mice; Neutralization Tests; Swine; Thailand |
Abstract |
|
Address |
|
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0006-2324 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:4400462 |
Approved |
no |
Call Number |
Equine Behaviour @ team @ |
Serial |
2728 |
Permanent link to this record |
|
|
|
Author |
Touma, C.; Palme, R.; Sachser, N. |
Title |
Analyzing corticosterone metabolites in fecal samples of mice: a noninvasive technique to monitor stress hormones |
Type |
Journal Article |
Year |
2004 |
Publication |
Hormones and Behavior |
Abbreviated Journal |
Horm Behav |
Volume |
45 |
Issue |
1 |
Pages |
10-22 |
Keywords |
Adrenal Cortex/drug effects; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone/pharmacology; Analysis of Variance; Animals; Circadian Rhythm; Corticosterone/*analysis/metabolism; Dexamethasone/pharmacology; Feces/*chemistry; Female; Immunoenzyme Techniques/*methods; Male; Mice; Mice, Inbred C57BL; Models, Animal; Reproducibility of Results; Stress, Psychological/*metabolism |
Abstract |
In small animals like mice, the monitoring of endocrine functions over time is constrained seriously by the adverse effects of blood sampling. Therefore, noninvasive techniques to monitor, for example, stress hormones in these animals are highly demanded in laboratory as well as in field research. The aim of our study was to evaluate the biological relevance of a recently developed technique to monitor stress hormone metabolites in fecal samples of laboratory mice. In total, six experiments were performed using six male and six female mice each. Two adrenocorticotropic hormone (ACTH) challenge tests, two dexamethasone (Dex) suppression tests and two control experiments [investigating effects of the injection procedure itself and the diurnal variation (DV) of glucocorticoids (GCs), respectively] were conducted. The experiments clearly demonstrated that pharmacological stimulation and suppression of adrenocortical activity was reflected accurately by means of corticosterone metabolite (CM) measurements in the feces of males and females. Furthermore, the technique proved sensitive enough to detect dosage-dependent effects of the ACTH/Dex treatment and facilitated to reveal profound effects of the injection procedure itself. Even the naturally occurring DV of GCs could be monitored reliably. Thus, our results confirm that measurement of fecal CM with the recently established 5alpha-pregnane-3beta,11beta,21-triol-20-one enzyme immunoassay is a very powerful tool to monitor adrenocortical activity in laboratory mice. Since mice represent the vast majority of all rodents used for research worldwide and the number of transgenic and knockout mice utilized as animal models is still increasing, this noninvasive technique can open new perspectives in biomedical and behavioral science. |
Address |
Department of Behavioural Biology, University of Muenster, D-48149 Muenster, Germany. touma@uni-muenster.de |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
0018-506X |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:14733887 |
Approved |
no |
Call Number |
Equine Behaviour @ team @ |
Serial |
4084 |
Permanent link to this record |
|
|
|
Author |
Crosby, M.B.; Zhang, J.; Nowling, T.M.; Svenson, J.L.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
Title |
Inflammatory modulation of PPAR gamma expression and activity |
Type |
Journal Article |
Year |
2006 |
Publication |
Clinical immunology |
Abbreviated Journal |
Clin Immunol |
Volume |
118 |
Issue |
2-3 |
Pages |
276-283 |
Keywords |
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 |
Abstract |
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. |
Address |
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA |
Corporate Author |
|
Thesis |
|
Publisher |
|
Place of Publication |
|
Editor |
|
Language |
English |
Summary Language |
|
Original Title |
|
Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
Series Volume |
|
Series Issue |
|
Edition |
|
ISSN |
1521-6616 |
ISBN |
|
Medium |
|
Area |
|
Expedition |
|
Conference |
|
Notes |
PMID:16303334 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
67 |
Permanent link to this record |