共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Lu S Nishimura K Hossain MA Jisaka M Nagaya T Yokota K 《Applied biochemistry and biotechnology》2004,118(1-3):133-153
Although some eicosanoids serve as potent natural ligands to activate peroxisome proliferator-activated receptor (PPARγ),
the ability of adipocytes to produce eicosanoids and regulate PPARγ remains unclear. Here, adipogenic 3T3-L1 cells were employed
to determine the gene expression of isoforms of biosynthetic enzymes in the arachidonate cyclooxygenase (COX) pathway and
the synthesis of prostaglandins (PGs). The expression of COX-2 was induced transiently in a biphasic manner upon the triggering
of the differentiation and maturation phases while COX-1 was constitutive. The exclusive expression of lipocalin-type PGD
synthase occurred and gradually increased during the maturation process along with the stable expression of PPARγ. Moreover,
we confirmed the formation of PGD2 from arachidonic acid by the mature adipocytes, suggesting conversion into PGJ2 derivatives. Even though cytosolic and membrane-associated subtypes of PGE synthase were expressed at relatively constant
levels, the ability of preadipocytes to produce PGE2 was greater than that of mature adipocytes in the cell response. The treatment of the mature adipocytes with exogenous PGD2, 15-deoxy-Δ12,14-PGJ2 and PGE2, in the presence of aspirin, enhanced the adipogenesis. These findings imply the specific roles of prostanoids produced by
the mature adipocytes in the maintenance of terminal differentiation through an autocrine control mechanism. 相似文献
3.
F. Xu C.-C. Yang C. Gomillion K. J. L. Burg 《Applied biochemistry and biotechnology》2010,160(1):197-212
Proinflammatory cytokines such as tumor necrosis factor (TNF) α are well known to inhibit adipocyte differentiation. TNF-α
triggers ceramide synthesis through binding of TNF-α to its p55 receptor. Therefore, ceramide is implicated in many of the
multiple signaling pathways initiated by TNF-α. In breast tissue engineering, it is important to know how to modulate adipocyte
differentiation of the stem cells with exogenous additives like ceramide in vitro. We hypothesized that stem cell adipogenesis could be retained in TNF-α-treated preadipocytes in which ceramide synthesis
was blocked and that exogenous ceramide could inhibit adipocyte differentiation. We first studied the effect of ceramide synthase
inhibitor, Fumonisin B2, on the adipogenesis of murine mesenchymal stem cells (D1 cells), treated with TNF-α. We then studied
the effect of specific exogenous C6-ceramide on D1 cell viability and differentiation. It was found that 1 ng/ml of TNF-α
significantly inhibited D1 cell adipogenesis. Cells treated with 5 μM of Fumonisin B2 were able to undergo adipogenesis, even
when treated with TNF-α. High concentrations of exogenous C6-ceramide (>50 μM) had an inhibitory effect, not only on the pre-confluent
proliferation of the D1 cells but also on the post-confluent cell viability. High concentrations of C6-ceramide (>50 μM) also
inhibited mitotic clonal expansion when D1 cell differentiation was induced by the addition of an adipogenic hormonal cocktail.
C6-ceramide at low concentrations (10–25 μM) inhibited lipid production in D1 cells, demonstrated by decreased levels of both
total triglyceride content and specific fatty acid composition percentages. Genetic expression of peroxisome proliferator-activated
receptor (PPAR) γ and aP2 in D1 cells was reduced by C6-ceramide treatment. CCAAT/enhancer-binding protein (C/EBP) β levels
in D1 cells were reduced by C6-ceramide treatment during early differentiation; PPARγ and aP2 protein levels were reduced
at terminal differentiation. C6-ceramide at lower concentrations also decreased lipid accumulation of differentiating D1 cells.
Our results suggest that ceramide synthase inhibitor retains the adipogenic potential of TNF-α-treated mesenchymal stem cells,
while exogenous ceramide at lower concentrations inhibit the adipogenesis of mesenchymal stem cells. Ceramide, therefore,
could be a modulator candidate in breast tissue engineering strategies. 相似文献
4.
5.
心血管疾病(CVD)是类风湿关节炎(RA)患者死亡的重要原因之一,脂代谢紊乱与CVD发生有密切关联,因而有必要对RA和药物治疗导致的脂代谢改变进行探讨。该研究采用胶原诱导法(CIA)构建关节炎模型,引入多维质谱鸟枪法开展血清脂质分析,检测了血清中105种脂质分子,发现模型大鼠体内7种磷脂酰肌醇、15种鞘磷脂、5种神经酰胺、10种磷脂酰胆碱和2种溶血磷脂酰胆碱异常上调,环氧酶-2(COX-2)抑制剂可部分修复紊乱的脂代谢,但对5种磷脂酰胆碱和1种溶血磷脂酰胆碱具有异常调控作用。该研究从脂质分子水平探讨了RA及COX-2抑制剂对脂代谢的干预作用,可以为RA的心血管风险研究提供信息。 相似文献
6.
Flavonol acylglycosides from flower of Albizia julibrissin and their inhibitory effects on lipid accumulation in 3T3-L1 cells 总被引:1,自引:0,他引:1
Obesity is a serious health problem worldwide. We investigated the anti-obesity effect of the flower of Albizia julibrissin DURAZZ. (Leguminosae). A 90% EtOH extract of the flower inhibited adipogenesis in 3T3-L1 preadipocytes, as well as the activity of glycerol-3-phosphate dehydrogenase (GPDH) activity. New flavonol acylglycosides (1-4) and eighteen known compounds (5-22) were isolated by bioassay-directed fractionation. These new glycosides were elucidated to be 3″-(E)-p-coumaroylquercitrin (1), 3″-(E)-feruloylquercitrin (2), 3″-(E)-cinnamoylquercitrin (3), and 2″-(E)-cinnamoylquercitrin (4) on the basis of spectroscopic and chemical analysis. These compounds inhibited adipogenesis in 3T3-L1 preadipocytes. In particular, 2 exhibited potent inhibitory effects on triglyceride accumulation. Furthermore, GPDH activity was inhibited by 2. Additionally, 2 inhibited glucose uptake in 3T3-L1 adipocytes. These results indicate that the 90% EtOH extract and compounds isolated from the flower of A. julibrissin inhibit adipogenesis in 3T3-L1 preadipocytes and may have anti-obesity effect through the inhibition of preadipocyte differentiation. 相似文献
7.
8.
The discovery of selective cyclooxygenase-2 (COX-2) inhibitors represents a major achievement of the efforts over the past few decades to develop therapeutic treatments for inflammation. To gain insights into designing new COX-2-selective inhibitors, we address the energetic and structural basis for the selective inhibition of COX isozymes by means of a combined computational protocol involving docking experiment, force field design for the heme prothetic group, and free energy perturbation (FEP) simulation. We consider both COX-2- and COX-1-selective inhibitors taking the V523I mutant of COX-2 to be a relevant structural model for COX-1 as confirmed by a variety of experimental and theoretical evidences. For all COX-2-selective inhibitors under consideration, we find that free energies of binding become less favorable as the receptor changes from COX-2 to COX-1, due to the weakening and/or loss of hydrogen bond and hydrophobic interactions that stabilize the inhibitors in the COX-2 active site. On the other hand, COX-1-selective oxicam inhibitors gain extra stabilization energy with the change of residue 523 from valine to isoleucine because of the formations of new hydrogen bonds in the enzyme-inhibitor complexes. The utility of the combined computational approach, as a valuable tool for in silico screening of COX-2-selective inhibitors, is further exemplified by identifying the physicochemical origins of the enantiospecific selective inhibition of COX-2 by -substituted indomethacin ethanolamide inhibitors. 相似文献
9.
Liu Q Hong IP Ahn MJ Yoo HS Han SB Hwang BY Lee MK 《Natural product communications》2011,6(12):1839-1841
Inhibition of adipocytes differentiation is suggested to be an important strategy for prevention and/or treatment of obesity. In our present study, Cordyceps militaris showed significant inhibitory activity on adipocyte differentiation in 3T3-L1 preadipocytes as assessed by measuring fat accumulation using Oil Red O staining. Activity-guided fractionation led to the isolation of cordycepin (1), guanosine (2) and tryptophan (3) as active compounds. All the three compounds were more effective in the prevention of early stage of adipogenesis than in lipolysis. In addition, combinational treatment of three compounds significantly increased anti-adipogenic activity. 相似文献
10.
Narjara Gonzalez Suarez Sahily Rodriguez Torres Amira Ouanouki Layal El Cheikh-Hussein Borhane Annabi 《Molecules (Basel, Switzerland)》2021,26(6)
Obese subjects have an increased risk of developing triple-negative breast cancer (TNBC), in part associated with the chronic low-grade inflammation state. On the other hand, epidemiological data indicates that increased consumption of polyphenol-rich fruits and vegetables plays a key role in reducing incidence of some cancer types. Here, we tested whether green tea-derived epigallocatechin-3-gallate (EGCG) could alter adipose-derived mesenchymal stem cell differentiation into adipocytes, and how this impacts the secretome profile and paracrine regulation of the TNBC invasive phenotype. Here, cell differentiation was performed and conditioned media (CM) from preadipocytes and mature adipocytes harvested. Human TNBC-derived MDA-MB-231 real-time cell migration was performed using the exCELLigence system. Differential gene arrays and RT-qPCR were used to assess gene expression levels. Western blotting was used to assess protein expression and phosphorylation status levels. In vitro vasculogenic mimicry (VM) was assessed with Matrigel. EGCG was found to inhibit the induction of key adipogenic biomarkers, including lipoprotein lipase, adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. Increased TNBC-derived MDA-MB-231 cell chemotaxis and vasculogenic mimicry were observed in response to mature adipocytes secretome, and this was correlated with increased STAT3 phosphorylation status. This invasive phenotype was prevented by EGCG, the JAK/STAT inhibitors Tofacitinib and AG490, as well as upon STAT3 gene silencing. In conclusion, dietary catechin-mediated interventions could, in part through the inhibition of adipogenesis and modulation of adipocytes secretome profile, prevent the onset of an obesogenic environment that favors TNBC development. 相似文献
11.
Mi Eun Lee So Ra Kim Seungkoo Lee Yu-Jin Jung Sun Shim Choi Woo Jin Kim Jeong A Han 《Experimental & molecular medicine》2012,44(9):536-544
It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1. 相似文献
12.
Pandurangan Subash-Babu Hussah Mohammed Alowaidh Laila Naif Al-Harbi Ghalia Shamlan Amal A. Aloud Sahar Abdulaziz AlSedairy Ali Abdullah Alshatwi 《Molecules (Basel, Switzerland)》2022,27(4)
Excessive storage of lipids in visceral or ectopic sites stimulates adipokine production, which attracts macrophages. This process determines the pro- and anti-inflammatory response regulation in adipose tissue during obesity-associated systemic inflammation. The present study aimed to identify the composition of Ocimum basilicum L. (basil) seed extract and to determine its bio-efficacy on adipocyte thermogenesis or fatty acid oxidation and inhibition of lipid accumulation and adipokine secretion. Ocimum basilicum L. seed methanol extract (BSME) was utilized to analyze the cytotoxicity vs. control; lipid accumulation assay (oil red O and Nile red staining), adipogenesis and mitochondrial-thermogenesis-related gene expression vs. vehicle control were analyzed by PCR assay. In addition, vehicle control and BSME-treated adipocytes condition media were collected and treated with lipopolysaccharide (LPS)-induced macrophage to identify the macrophage polarization. The results shown that the active components present in BSME did not produce significant cytotoxicity in preadipocytes or macrophages in the MTT assay. Furthermore, oil red O and Nile red staining assay confirmed that 80 and 160 μg/dL concentrations of BSME effectively arrested lipid accumulation and inhibited adipocyte maturation, when compared with tea polyphenols. Gene expression level of adipocyte hyperplasia (CEBPα, PPARγ) and lipogenesis (LPL)-related genes have been significantly (p ≤ 0.05) downregulated, and mitochondrial-thermogenesis-associated genes (PPARγc1α, UCP-1, prdm16) have been significantly (p ≤ 0.001) upregulated. The BSME-treated, maturing, adipocyte-secreted proteins were detected with a decreased protein level of leptin, TNF-α, IL-6 and STAT-6, which are associated with insulin resistance and macrophage recruitment. The “LPS-stimulated macrophage” treated with “BSME-treated adipocytes condition media”, shown with significant (p ≤ 0.001) decrease in metabolic-inflammation-related proteins—such as PGE-2, MCP-1, TNF-α and NF-κB—were majorly associated with the development of foam cell formation and progression of atherosclerotic lesion. The present findings concluded that the availability of active principles in basil seed effectively inhibit adipocyte hypertrophy, macrophage polarization, and the inflammation associated with insulin resistance and thrombosis development. Ocimum basilicum L. seed may be useful as a dietary supplement to enhance fatty acid oxidation, which aids in overcoming metabolic complications. 相似文献
13.
Kleban J Mikes J Szilárdiová B Koval J Sacková V Solár P Horváth V Hofmanová J Kozubík A Fedorocko P 《Photochemistry and photobiology》2007,83(5):1174-1185
One proposal to increase the efficiency of photodynamic therapy (PDT) is to accompany photosensitization with other treatment modalities, including modulation of arachidonic acid (AA) metabolism. The aim of this study was to evaluate the effectiveness of a combined modality approach employing 48 and 24 h pretreatment with various inhibitors of lipoxygenase (LOX; nordihydroguaiaretic acid, esculetin, AA-861, MK-886 and baicalein), cyclooxygenase (COX; diclofenac, flurbiprofen, ibuprofen, indomethacin, SC-560 and rofecoxib) and cytochrome P450-monooxygenase (proadifen) pathways, followed by hypericin-mediated PDT. Cytokinetic parameters like MTT assay, adherent and floating cell numbers, viability and cell cycle distribution analysis were examined 24 h after hypericin activation. Pretreatment of human colon cancer cells HT-29 prior to PDT with 5-LOX inhibitor MK-886 as well as 5, 12-LOX and 12-LOX inhibitors (esculetin and baicalein, respectively) resulted in significant and dose-dependent effects on all parameters tested. Pretreatment with diclofenac, flurbiprofen, ibuprofen and indomethacin, the nonspecific COX inhibitors, promoted hypericin-mediated PDT, but these effects were probably COX-independent. In contrast, application of SC-560 and rofecoxib, specific inhibitors of COX-1 and COX-2, respectively, attenuated PDT. Inhibition of P450 monooxygenase with proadifen implied also the significance of this metabolic pathway in cell survival and cell resistance to hypericin photocytotoxicity. In conclusion, our results testify that application of diverse inhibitors of AA metabolism may have different consequences on cellular response to hypericin-mediated PDT and that some of them could be considered for potentiation of PDT. 相似文献
14.
15.
Xue-Ping Chu Qing-Fa Zhou Shen Zhao Fei-Fei Ge Mian Fu Jia-Peng Chen Tao Lu 《中国化学快报》2013,24(2):120-122
A group of 3-amino-2-pyrones were synthesized and their biological activities were evaluated for inhibiting cyclooxygenase(COX) activity.This study has led to the identification of COX-1-selective inhibitors.Among the tested compounds,the compound 5j exhibited the most potent COX-1 inhibitory activity(IC50 = 19.32μg/mL) and COX-1 selectivity index(SI = 41.98). 相似文献
16.
Cyclooxygenase (COX)-2 inhibitors are known to be used as chemopreventative agents against certain malignancies. Thus far, there has been very limited information on whether COX-2 inhibitors protect against chronic narrow-band UVB (NB-UVB)-induced immunosuppression. The present study investigated the effect of nonselective and specific COX-2 inhibitors, indomethacin and celecoxib, on epidermal Ia+ Langerhans cells (LCs) and Thy-1+ dendritic epidermal T cells (DETCs) in mice irradiated with NB-UVB. Sixty female BALB/c mice were divided randomly into the control group (sham) and the experimental groups (irradiated with NB-UVB for 17 weeks, further divided into five groups according to the diets containing different concentrations of either COX-2 inhibitors). Alterations in the density and morphology of epidermal Ia+ LCs and Thy-1+ DETCs in mice were documented using fluorescence microscopy. Chronic NB-UVB irradiation substantially decreased the density and altered the morphology of the epidermal Ia+ LCs and Thy-1+ DETCs in control mice. The dietary supplementation of both COX-2 inhibitors displayed a dosage-dependent protective effect on the murine dendritic cells irradiated by NB-UVB. In conclusion, COX-2 inhibitors protected against chronic NB-UVB-induced density and morphologic changes in epidermal Ia+ LCs and Thy-1+ DETCs in mice. 相似文献
17.
M. R. Yadav S. T. Shirude A. Parmar R. Balaraman R. Giridhar 《Chemistry of Heterocyclic Compounds》2006,42(8):1038-1045
2,3-Diaryl-4(3H)-quinazolinones containing various substituents on diaryl rings have been synthesized and evaluated for their
cyclooxygenase-2 inhibitory activity by the colorimetric COX (ovine) inhibitor screening assay and anti-inflammatory activity
by the carrageenan-induced rat paw edema assay. 2-(4-Nitrophenyl)-3-(4-tolyl)-4(3H)-quinazolinone showed a maximum COX-2 inhibition
of 27.72% at 22 μM concentration in the present series and exhibited a mild anti-inflammatory activity at a dose of 50 mg/kg
in carrageenan-induced rat paw edema assay.
Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1198–1205, August, 2006. 相似文献
18.
Bharatham K Bharatham N Kwon YJ Lee KW 《Journal of computer-aided molecular design》2008,22(12):925-933
Allosteric inhibition of protein tyrosine phosphatase 1B (PTP1B), has paved a new path to design specific inhibitors for PTP1B,
which is an important drug target for the treatment of type II diabetes and obesity. The PTP1B1–282-allosteric inhibitor complex crystal structure lacks α7 (287–298) and moreover there is no available 3D structure of PTP1B1–298 in open form. As the interaction between α7 and α6–α3 helices plays a crucial role in allosteric inhibition, α7 was modeled
to the PTP1B1–282 in open form complexed with an allosteric inhibitor (compound-2) and a 5 ns MD simulation was performed to investigate the
relative orientation of the α7–α6–α3 helices. The simulation conformational space was statistically sampled by clustering
analyses. This approach was helpful to reveal certain clues on PTP1B allosteric inhibition. The simulation was also utilized
in the generation of receptor based pharmacophore models to include the conformational flexibility of the protein-inhibitor
complex. Three cluster representative structures of the highly populated clusters were selected for pharmacophore model generation.
The three pharmacophore models were subsequently utilized for screening databases to retrieve molecules containing the features
that complement the allosteric site. The retrieved hits were filtered based on certain drug-like properties and molecular
docking simulations were performed in two different conformations of protein. Thus, performing MD simulation with α7 to investigate
the changes at the allosteric site, then developing receptor based pharmacophore models and finally docking the retrieved
hits into two distinct conformations will be a reliable methodology in identifying PTP1B allosteric inhibitors.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
19.
Nishimura K Tsumagari H Morioka A Yamauchi Y Miyashita K Lu S Jisaka M Nagaya T Yokota K 《Applied biochemistry and biotechnology》2002,102(1-6):239-250
The arachidonate cascade includes the cyclooxygenase (COX) pathway to form prostanoids and the lipoxygenase (LOX) pathway
to generate several oxygenated fatty acids, collectively called eicosanoids. Eicosanoids are suggested to play a dual role
in regulating cell survival and apoptosis in various types of cells through an unknown mechanism. We found apoptosis in cultured
Madin-Darby canine kidney (MDCK) cells treated with 12-O-tetradecanoylphorbol β-acetate (TPA), a potent tumor promoter, and nordihydroguaiaretic acid (NDGA), a LOX inhibitor. The
effect of TPA was synergistically stimulated along with NDGA. Aspirin, a COX inhibitor, was not effective. The target of NDGA
might be different from the mechanism involving a LOX activity in some kinds of carcinoma cells because the increased expression
of 12-LOX was not detected in MDCK cells treated with TPA. Caspase and poly(ADP-ribose) metabolites were found to be involved
in the signal transduction pathway of the TPA- and NDGA-induced apoptosis in MDCK cells. Alternatively, hydrogen peroxide-induced
apoptosis was not affected by NDGA. Thus, the TPA-induced response involved the mechanism independent of the oxidative stress.
Obesity is a risk factor for severe diseases including noninsulin-dependent diabetes and atherosclerosis characterized by
the changes of cell properties of adipocytes. We found that conjugated linolenic acid from bitter gourd was able to induce
apoptosis in mouse preadipogenic 3T3-L1 cells. The findings provide the potential use of conjugated fatty acids to regulate
obesity. 相似文献
20.
El-Moselhy MA Abdel-Hamid NM Abdel-Raheim SR 《Applied biochemistry and biotechnology》2009,152(3):449-459
Despite the fact that dietary habits and lifestyles are incredibly advancing, gastric ulceration is still a terrible complaint.
Extensive use of non-steroidal anti-inflammatory drugs (NSAIDs) and alcohol, in addition to stress, are all predisposing factors
for ulcers. Most medical treatments are always time consuming and not efficient or satisfactory to the patients. Cardiovascular
patients always need NSAIDs, or mostly cannot quit alcohols, while using many cardiovascular drugs. We aim to study a possible
benefit of a common nitrogen oxide donor, anti-anginal drug, nicorandil [N-(2-hydroxyethyl) nicotinamide nitrate ester], in managing acute gastric ulcers through studying its effect on some relevant
intermediates to ulcerogenesis as lipid peroxidation, tumor necrosis factor-alpha (TNF-α), and nitric oxide (NO). In addition,
gastric mucosal histology was studied to pursue the drug effects on tissue level. Our study revealed that both indomethacin
and alcohol induced gastric ulcer mainly through up-regulation of gastric mucosal lipid peroxidation, local tissue inflammation,
leukocytic infiltration, and necrosis. Both ulcerogens significantly elevated TNF-α and decreased NO, initiating ulcer formation.
Nicorandil pretreatment depicted a higher preventive index in indomethacin- (89.8%) and alcohol-induced (77.7%) acute ulceration.
On the tissue level, it also protected the gastric mucosa combating leukocyte infiltration and tissue congestion. Nicorandil
protected tissue necrosis through decreasing oxidative stress, elevating NO levels, and down-regulating the ulcerogen-induced
TNF-α elevation and improved sub-mucosal blood supply. We conclude that nicorandil may be a suitable bimodal treatment for
cardiovascular patients who are at high risk of gastric ulcers by using variable analgesics to alleviate possible cardiac
pain episodes, and probably frequent doses will offer a more established and long-lasting protection. 相似文献