共查询到20条相似文献,搜索用时 15 毫秒
1.
Pérez-Ortiz JM Tranque P Vaquero CF Domingo B Molina F Calvo S Jordán J Ceña V Llopis J 《The Journal of biological chemistry》2004,279(10):8976-8985
The glitazones or thiazolidinediones are ligands of the peroxisome proliferator-activated receptor gamma (PPARgamma). The glitazones are used in the treatment of diabetes, regulate adipogenesis, inflammation, cell proliferation, and induce apoptosis in several cancer cell types. High grade astrocytomas are rapidly growing tumors derived from astrocytes, for which new treatments are needed. We determined the effects of two glitazones, ciglitazone and the therapeutic rosiglitazone, on the survival of serum-deprived primary rat astrocytes and glioma cell lines C6 and U251, which were assessed by the methylthiazolyl tetrazolium assay and lactate dehydrogenase release. Rosiglitazone (5-20 microM) decreased survival of glioma cells without affecting primary astrocytes, whereas ciglitazone at 20 microM was toxic for both cell types. Ciglitazone at 10 microM was cytoprotective for primary astrocytes but toxic to glioma cells. Cell death induced by ciglitazone, but not rosiglitazone, presented apoptotic features (Hoechst staining and externalization of phosphatidylserine). Two mechanisms to explain cytotoxicity were investigated: activation of PPARgamma and production of reactive oxygen species (ROS). PPARgamma does not seem to be the main mechanism involved, because the order of efficacy for cytotoxicity, ciglitazone > rosiglitazone, was inverse of their reported affinities for activating PPARgamma. In addition, GW9662, an inhibitor of PPARgamma, only slightly attenuated cytotoxicity. However, the rapid increase in ROS production and the marked reduction of cell death with the antioxidants ebselen and N-acetylcysteine, indicate that ROS have a key role in glitazone cytotoxicity. Ciglitazone caused a dose-dependent and rapid loss (in minutes) of mitochondrial membrane potential in glioma cells. Therefore, mitochondria are a likely source of ROS and early targets of glitazone cytotoxicity. Our results highlight the potential of rosiglitazone and related compounds for the treatment of astrogliomas. 相似文献
2.
Lee MW Kim DS Kim HR Kim HJ Yang JM Ryu S Noh YH Lee SH Son MH Jung HL Yoo KH Koo HH Sung KW 《Biochemical and biophysical research communications》2012,417(1):552-557
Peroxisome proliferator-activated receptor γ (PPARγ) regulates multiple signaling pathways, and its agonists induce apoptosis in various cancer cells. However, their role in cell death is unclear. In this study, the relationship between ciglitazone (CGZ) and PPARγ in CGZ-induced cell death was examined. At concentrations of greater than 30 μM, CGZ, a synthetic PPARγ agonist, activated caspase-3 and induced apoptosis in T98G cells. Treatment of T98G cells with less than 30 μM CGZ effectively induced cell death after pretreatment with 30 μM of the PPARγ antagonist GW9662, although GW9662 alone did not induce cell death. This cell death was also observed when cells were co-treated with CGZ and GW9662, but was not observed when cells were treated with CGZ prior to GW9662. In cells in which PPARγ was down-regulated cells by siRNA, lower concentrations of CGZ (<30 μM) were sufficient to induce cell death, although higher concentrations of CGZ (≥30 μM) were required to induce cell death in control T98G cells, indicating that CGZ effectively induces cell death in T98G cells independently of PPARγ. Treatment with GW9662 followed by CGZ resulted in a down-regulation of Akt activity and the loss of mitochondrial membrane potential (MMP), which was accompanied by a decrease in Bcl-2 expression and an increase in Bid cleavage. These data suggest that CGZ is capable of inducing apoptotic cell death independently of PPARγ in glioma cells, by down-regulating Akt activity and inducing MMP collapse. 相似文献
3.
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a naturally occurring cyclopentenone metabolite of prostaglandin D2 (PGD2) and is known as a specific potent ligand for the peroxisome proliferators activator receptor-γ (PPARγ). 15d-PGJ2 inhibits cell growth and induces apoptosis in a number of different cancer cells. However, the underlying mechanism by which 15d-PGJ2 induces cell death remains to be defined. The present study was undertaken to determine the effect of 15d-PGJ2 on cell death in A172 human glioma cells. 15d-PGJ2 caused reactive oxygen species (ROS) generation. 15d-PGJ2-induced ROS production and cell death were prevented by the antioxidant N-acetylcysteine. Activation of mitogen-activated protein kinases (MAPK) was not observed in cells treated with 15d-PGJ2 and inhibitors of MAPK subfamilies also were not effective in preventing 15d-PGJ2-induced cell death. 15d-PGJ2 treatment caused mitochondrial dysfunction, as evidenced by depolarization of mitochondrial membrane potential. 15d-PGJ2 induced caspase activation at 24 h of treatment, but the 15d-PGJ2-induced cell death was not prevented by caspase inhibitors. The antiapoptotic protein XIAP levels and release of apoptosis inducing factor (AIF) into the cytosol were not altered by 15d-PGJ2 treatment. Taken together, these findings indicate that 15d-PGJ2 triggers cell death through a caspase-independent mechanism and ROS production and disruption of mitochondrial membrane potential play an important role in the 15d-PGJ2-induced cell death in A172 human glioma cells. 相似文献
4.
Pioglitazone, a synthetic ligand for PPARγ, induces apoptosis in RB-deficient human colorectal cancer cells 总被引:1,自引:0,他引:1
Lee CJ Han JS Seo CY Park TH Kwon HC Jeong JS Kim IH Yun J Bae YS Kwak JY Park JI 《Apoptosis : an international journal on programmed cell death》2006,11(3):401-411
No published data are available about the expression of peroxisome proliferator-activated receptor γ (PPARγ) and the role
of PPARγ in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to
investigate whether PPARγ is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying
the effect of pioglitazone, a synthetic ligand for PPARγ, on cell growth in these cell lines. RT-PCR and Western blot analysis
showed that both human CRC cell lines expressed PPARγ mRNA and protein. Pioglitazone inhibited the cell growth of both cell
lines through G2/M phase block and apoptosis. In addition, pioglitazone caused a down-regulation of the X chromosome-linked
inhibitor of apoptosis (XIAP), Bcl-2, and cyclooxygenase-2 (COX-2) under conditions leading to PPARγ down-regulation. These
results suggest that pioglitazone may have therapeutic relevance or significance in the treatment of human CRC, and the down-regulation
of XIAP, Bcl-2, and COX-2 may contribute to pioglitazone-induced apoptosis in these and other RB-deficient cell lines and
tumors. 相似文献
5.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor modulating a variety of biological functions including cancer cell proliferation and differentiation. However, the role of PPARgamma and its ligands in tumor invasion is unclear. To evaluate a possible role for PPARgamma ligands in tumor invasion, we examined whether PPARgamma agonists including pioglitazone, troglitazone, rosiglitazone, and ciglitazone could affect the activity of matrix metalloproteinases (MMPs) in the HT1080 cell line, a well-studied and well-characterized cell line for MMP research. The gelatin zymography assay showed that ciglitazone activated pro-MMP-2 significantly. In addition, ciglitazone increased the expression of MMP-2, which was accompanied by an increase of membrane type 1-MMP (MT1-MMP) expression. The PPARgamma antagonist, GW9662 attenuated the ciglitazone-induced PPARgamma activation but it did not affect the pro-MMP2 activation by ciglitazone, suggesting that the action of ciglitazone on the pro-MMP-2 activation bypassed the PPARgamma pathway. Antioxidants and various inhibitors of signal transduction were used to investigate the mechanism of ciglitazone-induced pro-MMP-2 activation. We found that the sustained production of reactive oxygen species (ROS) was required for pro-MMP-2 activation by ciglitazone. We also found that PB98059, an inhibitor of MEK-ERK, significantly blocked ciglitazone-induced pro-MMP-2 activation and that extracellular signal-regulated kinase (ERK) was hyperphosphorylated by ciglitazone. Moreover, cell invasion was significantly increased by ciglitazone in the HT1080 cell lines, whereas cell motility was not affected. This study suggests that ciglitazone-induced pro-MMP-2 activation increases PPARgamma-independent tumor cell invasion through ROS production and ERK activation in some types of cancer cells. 相似文献
6.
Hampel JK Brownrigg LM Vignarajah D Croft KD Dharmarajan AM Bentel JM Puddey IB Yeap BB 《Prostaglandins, leukotrienes, and essential fatty acids》2006,74(5):283-293
We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARgamma2 gene expression. 相似文献
7.
Stephane Renauld Karine Tremblay Siham Ait-Benichou Maxime Simoneau-Roy Hugo Garneau Olivier Staub Ahmed Chraïbi 《The Journal of membrane biology》2010,236(3):259-270
Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists used to treat type 2 diabetes.
TZD treatment induces side effects such as peripheral fluid retention, often leading to discontinuation of therapy. Previous
studies have shown that PPARγ activation by TZD enhances the expression or function of the epithelial sodium channel (ENaC)
through different mechanisms. However, the effect of TZDs on ENaC activity is not clearly understood. Here, we show that treating
Xenopus
laevis oocytes expressing ENaC and PPARγ with the TZD rosiglitazone (RGZ) produced a twofold increase of amiloride-sensitive sodium
current (Iam), as measured by two-electrode voltage clamp. RGZ-induced ENaC activation was PPARγ-dependent since the PPARγ antagonist
GW9662 blocked the activation. The RGZ-induced Iam increase was not mediated through direct serum- and glucocorticoid-regulated kinase (SGK1)-dependent phosphorylation of
serine residue 594 on the human ENaC α-subunit but by the diminution of ENaC ubiquitination through the SGK1/Nedd4-2 pathway.
In accordance, RGZ increased the activity of ENaC by enhancing its cell surface expression, most probably indirectly mediated
through the increase of SGK1 expression. 相似文献
8.
PPAR-gamma ligands up-regulate basic fibroblast growth factor-induced VEGF release through amplifying SAPK/JNK activation in osteoblasts 总被引:5,自引:0,他引:5
Yasuda E Tokuda H Ishisaki A Hirade K Kanno Y Hanai Y Nakamura N Noda T Katagiri Y Kozawa O 《Biochemical and biophysical research communications》2005,328(1):137-143
We previously reported that basic fibroblast growth factor (FGF-2) activates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates the VEGF release. In the present study, we investigated the effects of ciglitazone and pioglitazone, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands, on the VEGF release by FGF-2 in MC3T3-E1 cells. The FGF-2-induced VEGF release was significantly enhanced by ciglitazone. The amplifying effect of ciglitazone was dose-dependent between 0.1 and 10 microM. Pioglitazone had a similar effect on the VEGF release. GW9662, an antagonist of PPAR-gamma, reduced the effects of ciglitazone and pioglitazone. Ciglitazone or pioglitazone markedly enhanced the phosphorylation of SAPK/JNK induced by FGF-2 without affecting both the FGF-2-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. GW9662 markedly reduced the amplification by ciglitazone of the SAPK/JNK phosphorylation. Taken together, these results strongly suggest that PPAR-gamma ligands up-regulate FGF-2-stimulated VEGF release resulting from amplifying activation of SAPK/JNK in osteoblasts. 相似文献
9.
Adenosine A3 receptor (A3AR) is coupled to G proteins that are involved in a variety of intracellular signaling pathways and physiological functions. 2-Chloro-N 6-(3-iodobenzyl) adenosine-5??-N-methylcarboxamide (Cl-IB-MECA), an agonist of A3AR, has been reported to induce cell death in various cancer cells. However, the effect of CI-IB-MECA on glioma cell growth is not clear. This study was undertaken to examine the effect of CI-IB-MECA on glioma cell viability and to determine its molecular mechanism. CI-IB-MECA inhibited cell proliferation and induced cell death in a dose- and time-dependent manner. Treatment of CI-IB-MECA resulted in an increase in intracellular Ca2+ followed by enhanced reactive oxygen species (ROS) generation. EGTA and N-acetylcysteine (NAC) blocked the cell death induced by CI-IB-MECA, suggesting that Ca2+ and ROS are involved in the Cl-IB-MECA-induced cell death. Western blot analysis showed that CI-IB-MECA induced the down-regulation of extracellular signal-regulated kinases (ERK) and Akt, which was prevented by EGTA, NAC, and the A3AR antagonist MRS1191. Transfection of constitutively active forms of MEK, the upstream kinase of ERK, and Akt prevented the cell death. CI-IB-MECA induced caspase-3 activation and the CI-IB-MECA-induced cell death was blocked by the caspase inhibitors DEVD-CHO and z-VAD-FMK. In addition, expression of XIAP and Survivin were decreased in cells treated with Cl-IB-MECA. Collectively, these findings demonstrate that CI-IB-MECA induce a caspase-dependent cell death through suppression of ERK and Akt mediated by an increase in intracellular Ca2+ and ROS generation in human glioma cells. These suggest that A3AR agonists may be a potential therapeutic agent for induction of apoptosis in human glioma cells. 相似文献
10.
Han H Shin SW Seo CY Kwon HC Han JY Kim IH Kwak JY Park JI 《Apoptosis : an international journal on programmed cell death》2007,12(11):2101-2114
While tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising new agent for the treatment of
cancer, resistance to TRAIL remains a therapeutic challenge. Identifying agents to use in combination with TRAIL to enhance
apoptosis in leukemia cells would increase the potential utility of this agent as a therapy for leukemia. Here, we show that
15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand for peroxisome proliferator-activated receptor γ (PPARγ), can sensitize TRAIL-resistant leukemic HL-60
cells to TRAIL-induced apoptosis. The sensitization to TRAIL-induced apoptosis by 15d-PGJ2 was not blocked by a PPARγ inhibitor (GW9662), suggesting a PPARγ-independent mechanism. This process was accompanied by
activation of caspase-8, caspase-9, and caspase-3 and was concomitant with Bid and PARP cleavage. We observed significant
decreases in XIAP, Bcl-2, and c-FLIP after cotreatment with 15d-PGJ2 and TRAIL. We also observed the inhibition of Akt expression and phosphorylation by cotreatment with 15d-PGJ2 and TRAIL. Furthermore, inactivation of Akt by Akt inhibitor IV sensitized human leukemic HL-60 cells to TRAIL, indicating
a key role for Akt inhibition in these events. Taken together, these findings indicate that 15d-PGJ2 may augment TRAIL-induced apoptosis in human leukemia cells by down-regulating the expression and phosphorylation of Akt. 相似文献
11.
Keyhanian K Edalat R Oghalaei A Askary N Golshani A Salehi M Sarrami-Forooshani R Shokrgozar MA 《Molecular and cellular biochemistry》2007,304(1-2):199-205
Hepatocyte growth factor (HGF) has opposite biological activities in regulating apoptosis, also underlying molecular mechanisms
are not clearly defined. We investigated HGF ability to inhibit cell death, which was induced by Doxorubicin, a DNA damaging
agent. Also Survivin and XIAP mRNA levels were compared in HGF treated and non-treated cells. Cell proliferation and death
were assessed using MTT assay and dye exclusion tests. Quantitative real-time PCR was used to evaluate Survivin and XIAP expression
levels after treatment with HGF. ELISA was performed to quantify HGF secretion in the selected cancer cell lines media. HGF
appeared to have inhibitory effect on Doxorubicin induced cell death in all of the studied cell lines. It had minimal effect
on XAIP and Survivin expression levels in MRC-5, MOLT-4 and AGS cell lines; except for XIAP expression level in AGS cell line,
which was increased substantially after treatment. Surprisingly, in KG-1 cell line, XIAP and Survivin expression levels were
significantly reduced after HGF treatment. Although several members of IAP gene family are reported to play role in HGF mediated cytoprotective pathway, we showed that XIAP and Survivin do not seem to be involved. 相似文献
12.
Schwab M Reynders V Ulrich S Zahn N Stein J Schröder O 《Apoptosis : an international journal on programmed cell death》2006,11(10):1801-1811
Background: Butyrate, a potent histone deacetylase inhibitor, belongs to a promising new class of antineoplastic agents with the capacity
to induce apoptosis of cancer cells. However, the underlying mechanisms of action have yet not been elucidated. Aim: To further investigate the molecular events involved in butyrate-induced caspase-3 activation in Caco-2 wild-type, empty-vector
and dominant-negative PPARγ mutant cells along the signalling pathway. In this context, the involvement and up-regulation
of PPARγ was examined. Results: Stimulation of cells with butyrate resulted in increased expression of PPARγ mRNA, protein, and activity as well as phospho-p38
MAPK protein expression and caspase-3 activity. Arsenite, a direct stimulator of p38 MAPK, also led to an increased PPARγ
expression, thereby mimicking the effects of butyrate. In contrast, butyrate-mediated up-regulation of PPARγ was counteracted
by co-incubation with the p38 MAPK inhibitor SB203580. Treatment of cells with butyrate resulted in both increased caspase-8
and -9 activity and reduced expression of XIAP and survivin. However, butyrate-mediated effects on these apoptosis-regulatory
proteins leading to caspase-3 activation were almost completely abolished in Caco-2 dominant-negative PPARγ mutant cells.
Conclusions: Our data clearly unveil PPARγ as a key target in the butyrate-induced signalling cascade leading to apoptosis via caspase-3
in Caco-2 cells. 相似文献
13.
Background
Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines.Methodology/Principal Findings
Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21waf1/CIP1 and p27Kip1 in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism.Conclusions/Significance
Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers. 相似文献14.
15.
16.
The present study was undertaken to determine the molecular mechanism by which kaempferol induces cell death in human glioma
cells. Kaempferol resulted in loss of cell viability and inhibition of proliferation in a dose- and time-dependent manner,
which were largely attributed to cell death. Kaempferol caused an increase in reactive oxygen species (ROS) generation and
the kaempferol-induced cell death was prevented by antioxidants, suggesting that ROS generation is involved in kaempferol-induced
cell death. Kaempferol caused depolarization of mitochondrial membrane potential. Western blot analysis showed that kaempferol
treatment caused a rapid reduction in phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. The ERK inhibitor
U0126 and the Akt inhibitor LY984002 increased the kaempferol-induced cell death and overexpression of MEK, the upstream kinase
of ERK, and Akt prevented the cell death. The expression of anti-apoptotic proteins XIAP and survivin was down-regulated by
kaempferol and its effect was prevented by overexpression of MEK and Akt. Kaempferol induced activation of caspase-3 and kaempferol-induced
cell death was prevented by caspase inhibitors. Taken together, these findings suggest that kaempferol results in human glioma
cell death through caspase-dependent mechanisms involving down-regulation of XIAP and survivin regulating by ERK and Akt. 相似文献
17.
Phenotype transformation of corneal keratocyte to myofibroblast plays an important role in the wound healing process of cornea
and TGFβ is considered to be the most important mediator to induce myofibroblast trans-differentiation. Peroxisome proliferator-activated
receptors-γ (PPAR-γ) activation has been proved to exert anti-fibrotic effect in many tissues. In this study, we investigated
the effect of PPAR-γ agonist, pioglitazone, on myofibroblast transformation, extracellular matrix production and cell proliferation.
The results showed pioglitazone inhibited the TGFβ-driven myofibroblast differentiation, as determined by F-actin fluorescence
staining, α-smooth muscle actin-specific immunocytochemistry and western blot analysis. Pioglitazone also potently attenuated
TGFβ induced type I collagen and fibronectin mRNA and protein production. Moreover, pioglitazone showed inhibitory effect
on TGFβ induced cell proliferation. The irreversible PPAR-γ antagonist GW9662, partially reversed the inhibition of collagen
I and fibronectin expression but not myofibroblast transformation, suggesting both PPAR-γ dependent and PPAR-γ independent
mechanisms were involved in the action of pioglitazone. Therefore, our study indicates pioglitazone has a potential application
in therapy of corneal fibrosis and PPAR-γ might be a promising therapy target. 相似文献
18.
Differential responses of PPARalpha, PPARdelta, and PPARgamma reporter cell lines to selective PPAR synthetic ligands 总被引:5,自引:0,他引:5
Seimandi M Lemaire G Pillon A Perrin A Carlavan I Voegel JJ Vignon F Nicolas JC Balaguer P 《Analytical biochemistry》2005,344(1):8-15
To characterize the specificity of synthetic compounds for peroxisome proliferator-activated receptors (PPARs), three stable cell lines expressing the ligand binding domain (LBD) of human PPARalpha, PPARdelta, or PPARgamma fused to the yeast GAL4 DNA binding domain (DBD) were developed. These reporter cell lines were generated by a two-step transfection procedure. First, a stable cell line, HG5LN, expressing the reporter gene was developed. These cells were then transfected with the different receptor genes. With the help of the three PPAR reporter cell lines, we assessed the selectivity and activity of PPAR agonists GW7647, WY-14-643, L-165041, GW501516, BRL49653, ciglitazone, and pioglitazone. GW7647, L-165041, and BRL49653 were the most potent and selective agonists for hPPARalpha, hPPARdelta, and hPPARgamma, respectively. Two PPAR antagonists, GW9662 and BADGE, were also tested. GW9662 was a selective PPARgamma antagonist, whereas BADGE was a low-affinity PPAR ligand. Furthermore, GW9662 was a full antagonist on PPARgamma and PPARdelta, whereas it showed partial agonism on PPARalpha. We conclude that our stable models allow specific and sensitive measurement of PPAR ligand activities and are a high-throughput, cell-based screening tool for identifying and characterizing PPAR ligands. 相似文献