2.Expression of the Peroxisome-proliferator-activated Receptor-gamma in Human Gastric Cancer.
Dong Hui CHO ; Dong Gue SHIN ; Sung Gu KANG ; Sang Su PARK ; Jin YOON ; Il Myung KIM ; Seong Min YOON ; Yun Kyung LEE ; Yong Jik LEE ; Dae Hyun YANG ; Ik Hang CHO
Journal of the Korean Gastric Cancer Association 2006;6(4):250-256
PURPOSE: Recently, interest in peroxisome-proliferator-activated receptors (PPAR) has increased, although clinical studies of the effect of PPAR-gamma expression on gastric cancer have not been reported yet. In this study, we investigated the role of PPAR-gamma expression in gastric cancer patients. MATERIALS AND METHODS: One hundred twenty-eight (128) samples of both gastric cancer and normal tissues were obtained from 128 patients who had undergone at a curative gastrectomy at Seoul Medical Center from Jan. 2001 to Dec. 2005. PPAR-gamma expression was determined by using immunohistochemical staining, and the results were analyzed. The statistical analysis was based on clinicopathological findings and the differences in survival rates. RESULTS: The mean age of the patients was 61, and the male:female ratio was 1.9:1. PPAR-gamma expression was significantly higher in cancer tissues than in normal tissue (81.3% vs. 57.0%, P<0.001). There was insignificant difference between well and moderately differentiated types and poorly differentiated types in terms of the expression of PPAR-gamma (87.0% vs. 74.6%, P=0.074). In the univariate analysis the survival rate was significantly increased when PPAR-gamma was expressed in normal tissue (P=0.003). In the multivariate analysis, only the UICC TNM staging had significance related to the survival rate. CONCLUSION: The rate of PPAR-gamma expression was higher in cancer tissue than it was in normal tissue from gastric cancer patients. In the univariate analysis, PPAR-gamma expression in normal tissue had significance with respect to survival, but the multivariate analysis showed no such significance. Thus, we should further evaluate more cases to determine whether or not such a significance exists.
Gastrectomy
;
Humans*
;
Multivariate Analysis
;
Neoplasm Staging
;
Peroxisome Proliferator-Activated Receptors
;
Seoul
;
Stomach Neoplasms*
;
Survival Rate
4.Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration.
Jia Jia CAI ; Min Ting LIANG ; Wan Qing LI ; Wei Yun ZHANG ; Xiao LI ; Zhao Hui SUN
Chinese Journal of Preventive Medicine 2023;57(7):1068-1074
To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.
Humans
;
Carcinoma, Hepatocellular/pathology*
;
Ferroptosis
;
Liver Neoplasms/pathology*
;
Peroxisome Proliferator-Activated Receptors/genetics*
5.The Effect of PPAR gamma2 Pro12Ala Polymorphism on Diabetic Nephropathy in Type 2 Diabetes.
Dong Min KIM ; Hyun Lee KIM ; Bum Yun KIM ; Byung Chul SHIN ; Jong Hoon CHUNG ; Hak Yeon BAE ; Byung Rae LEE
Korean Journal of Nephrology 2004;23(5):729-737
BACKGROUND: Recently, the PPAR gamma2 Pro12Ala polymorphism has been associated with type 2 diabetes and diabetic nephropathy. In the present study, we investigated the association between Pro12Ala polymorphism and diabetic nephropathy in korean subjects. METHODS: A total of 180 patients with type 2 diabetes and 100 normal controls were enrolled in this studies. Screening for mutation at codon of PPAR gamma2 were carried out by PCR-RELP analysis. Also, we measured important covariables, such as duration of diabetes, blood pressure, renal function and serum lipids. RESULTS: In PCR-RELP, it showed that there were no difference in the PPAR gamma2 genotype frequencies between diabetic subjects (Pro/Pro: 80.5%, Pro/Ala: 19.5%) and normal controls (88%, 12%). However, it showed that there were significant difference in the PPAR gamma2 genotype frequencies between diabetic subjects with nephropathy (Pro/Pro: 74.5%, Pro/Ala: 25.5%) and diabetic subjects without nephropathy (87.8%, 12.2%) (p=0.040). In diabetic subjects, Pro/Ala genotypes were significantly different from Pro/Pro regarding serum creatinine, 24 hour proteinuria, systolic pressure, and LDL-cholesterol. In diabetic nephropathy, genotypes with Pro/Ala significantly increased serum creatinine (2.7+/-0.41 vs 1.7+/-0.68 mg/dL), 24hour urine protein (median+-SE: 1.9+/-1.02 vs 0.9+/-0.44 g/day), systolic pressure (161+/-27.8 vs 152+/-32.4 mmHg), LDL cholesterol (134+/-30.4 vs 125+/-20.0 mg/dL), and triglyceride (151+/-86.5 vs 135+/-60.9 mg/dL) than genotypes with Pro/Pro. CONCLUSION: Our results suggested that Pro12Ala Polymorphism of the PPAR gamma2 gene may be associated with diabetes with nephropathy in korean patients.
Blood Pressure
;
Cholesterol, LDL
;
Codon
;
Creatinine
;
Diabetic Nephropathies*
;
Genotype
;
Humans
;
Mass Screening
;
Peroxisome Proliferator-Activated Receptors*
;
Proteinuria
;
Triglycerides
6.Peroxisome Proliferator-Activated Receptor Gamma(PPAR-gamma) Agonist Improves Endothelial Function in Diabetic Patients with Metabolic Syndrome: Pivotal Role of NOx and Inflammation.
Jin Sin KHO ; Sung Ji PARK ; Sung Il IM ; Bong Ryong CHOI ; Choong Hwan KWAK ; Jin Yong HWANG
Korean Circulation Journal 2007;37(5):221-229
BACKGROUND AND OBJECTIVES: Nitric oxide (NO) is thought to have antiatherosclerotic properties. On the other hand, NO activity is reduced in patients with metabolic syndrome, and endothelial dysfunction is an important early sign of atherosclerosis in patients with metabolic syndrome. The aim of this study was to investigate the effect of pioglitazone on the endothelial function in terms of the plasma NOx (combined nitrate/nitrite), the circulating inflammatory markers and the autonomic nervous system. SUBJECTS AND METHODS: We randomized 40 subjects with metabolic syndrome, and they were assigned to receive 15 mg of pioglitazone per day (the PIO group, n=21) during 12 weeks or they were placed in the placebo group (the PLA group, n=19). We estimate the endothelial function by performing vascular ultrasound. The plasma NOx levels, the levels of the inflammatory markers and the GRK2 levels were measured. RESULTS: After 12 weeks of therapy, flow mediated dilation (FMD) was improved in the PIO group (from 6.7+/-6% to 11.7+/-5%, respectively: p<0.05), but not in the PLA group. The level of plasma NOx was increased in the PIO group (from 67.7+/-30 nmol/dL to 92.9+/-41 nmol/dL, respectively: p<0.001), but not in the PLA group. The plasma levels of hsCRP and IL-6 dropped significantly (from 2.6+/-2.3 mg/L to 1.2+/-1.3 mg/L and 1.7+/-2.1 pg/mL to 0.7+/-0.5 pg/mL, respectively: p<0.05) in the PIO group, but not in the PLA group. The levels of GRK2 (the PLA group from 0.0061+/-0.0023 ng to 0.0075+/-0.0031 ng, and the PIO group from 0.0024+/-0.002 ng to 0.0015+/-0.001 ng, p=ns) didn't dropped significantly. CONCLUSION: Administration of PPAR-gamma agonist in patients suffering with metabolic syndrome improves their endothelial function, enhances the production of NOx and reduces the proinflammatory markers, but this is not related to sympathetic regulation. PPAR-gamma agonist may be able to modulate the progression of atherosclerosis.
Atherosclerosis
;
Autonomic Nervous System
;
Hand
;
Humans
;
Inflammation*
;
Interleukin-6
;
Nitric Oxide
;
Peroxisome Proliferator-Activated Receptors
;
Peroxisomes*
;
Plasma
;
Ultrasonography
7.The variation of PPAR pathway molecules in the lung tissue of rats under hyperbaric oxygen exposure.
Pu YOU ; Jian YAO ; Xiao-Chen BAO ; Jun MA ; Shi ZHANG ; Yi-Qun FANG
Chinese Journal of Applied Physiology 2012;28(4):298-300
OBJECTIVETo study the expression pattern of peroxisome proliferator-activated receptor (PPAR) pathway molecules in rat lung tissue under hyperbaric oxygen exposure.
METHODSTwenty seven male SD rats were randomly divided into hyperbaric normoxia group (0.23 MPa air), hyperbaric oxygen treatment time series group (0.23 MPa oxygen, were exposed for 2 h, 4 h, 6 h or 8 h), continuous small flow of ventilation to maintain cabin O2 concentration > 99%. HE staining of lung tissue morphological changes and application oligo microarray to each time point lung were observed. Part of the PPAR pathway genes were validated by RT-PCR.
RESULTSCompared with hyperbaric normoxia group, the lung injury caused by hyperbaric oxygen treatment gradually deteriorated during the time series. Expression microarray analysis of gene ontology (Go) enrichment analysis results in a class of PPAR pathway class included multiple PPAR pathway molecule. RT-PCR results suggested that PPAR-8 and PPAR-Y were up-regulated in the lung tissue after a long time exposure to hyperbaric oxygen.
CONCLUSIONPro-longed hyperbaric oxygen exposure causing pulmonary oxygen toxicity can induce the activation of the PPAR pathway.
Animals ; Hyperbaric Oxygenation ; adverse effects ; Lung ; metabolism ; pathology ; Male ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction
9.Increased hepatic peroxisome proliferator-activated receptor coactivator-1α expression precedes the development of insulin resistance in offspring of rats from severe hyperglycemic mothers.
Jing-mei MA ; Chan-juan ZENG ; Li ZHANG ; Chong SHOU ; Hui-xia YANG
Chinese Medical Journal 2012;125(7):1224-1229
BACKGROUNDPrenatal hyperglycaemia may increase metabolic syndrome susceptibility of the offspring. An underlying component of the development of these morbidities is hepatic gluconeogenic molecular dysfunction. We hypothesized that maternal hyperglycaemia will influence her offsprings hepatic peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) expression, a key regulator of glucose production in hepatocytes.
METHODWe established maternal hyperglycaemia by streptozotocin injection to induce the maternal hyperglycaemic Wistar rat model. Offspring from the severe hyperglycemia group (SDO) and control group (CO) were monitored until 180 days after birth. Blood pressure, lipid metabolism indicators and insulin resistance (IR) were measured. Hepatic PGC-1α expression was analyzed by reverse transcription polymerase chain reaction and Western blotting. mRNA expression of two key enzymes in gluconeogenesis, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), were analyzed and compared.
RESULTSIn the SDO group, PGC-1α expression at protein and mRNA levels were increased, so were expression of G-6-Pase and PEPCK (P < 0.05). The above effects were seen prior to the onset of IR.
CONCLUSIONThe hepatic gluconeogenic molecular dysfunction may contribute to the metabolic morbidities experienced by this population.
Animals ; Female ; Hyperglycemia ; chemically induced ; physiopathology ; Insulin Resistance ; physiology ; Liver ; metabolism ; Male ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; RNA-Binding Proteins ; Rats ; Rats, Wistar ; Streptozocin ; toxicity ; Transcription Factors
10.Transporters and Nuclear Hormone Receptors associated with Cholesterol Metabolism in Gallbladder Epithelial Cells.
Hanyang Medical Reviews 2007;27(1):20-28
Bile is concentrated in the gallbladder, and is often supersaturated in terms of cholesterol concentration. Such high levels of cholesterol in gallbladder bile has clinical implications with respect to cholesterol gallstone formation. Gallbladder epithelial cells (GBEC) are exposed to high cholesterol concentrations on their apical surface. Therefore, GBEC are uniquely positioned to play an important role in modulating biliary cholesterol concentration. Recently, it has been documented that the key-transporter for polarized cholesterol and phospholipid efflux in GBEC is ATP-binding cassette transporter A1 (ABCA1) and liver X receptor alpha(LXR alpha)/retinoid X receptor (RXR) in the nucleus of GBEC which regulates ABCA1 expression. In addition, it also has been demonstrated that ligands of peroxisome proliferator-activated receptor alpha(PPARalpha) and PPARgamma modulate inflammation and affect ABCA1 expression in GBEC. This evidence proves that GBEC has a perfect system for cholesterol transport. We herein introduce the roles and mechanisms of ABCA1, ABCG5/ABCG8, scavenger receptor class B-I (SR-BI), LXRalpha/RXR, farnesoid X receptor (FXR), and PPARs related to cholesterol transport in GBEC with a review of our study experience and related literature.
Bile
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Cholesterol*
;
Epithelial Cells*
;
Gallbladder*
;
Gallstones
;
Inflammation
;
Ligands
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Liver
;
Metabolism*
;
Peroxisome Proliferator-Activated Receptors
;
Peroxisomes
;
PPAR gamma
;
Receptors, Cytoplasmic and Nuclear*
;
Receptors, Scavenger