scholarly journals Downregulation of mPGES-1 ExpressionviaEGR1 Plays an Important Role in Inhibition of Caffeine on PGE2Synthesis of HBx(+) Hepatocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yan Ma ◽  
Xiaoqian Wang ◽  
Nanhong Tang
Keyword(s):  
Molecular Biology ◽  
Promoter Activity ◽  
Inhibitory Effect ◽  
Hepatocyte Proliferation ◽  
Test Time ◽  
Limited Success ◽  
Caffeine Treatment ◽  
New Evidence ◽  
Time Point

We investigated the mechanism of caffeine in influencing HBx(+) hepatocytes to synthesize PGE2. The inhibitory effect of caffeine on hepatocyte proliferation increased with increasing caffeine concentrations (200–800 μM) and treatment times (1–7 days), which was first observed at the second test time point (caffeine treatment for 4 days). The inhibition of caffeine on the growth of HL7702-HBx and HepG2-HBx cells was most obvious at 800 μM caffeine and at caffeine treatment for 7 days. The PGE2secretion and the expression of mPGES-1 and EGR1 were downregulated, whereas PPARγexpression was upregulated. The mPGES-1 promoter activity of HBx(+) hepatocytes decreased more significantly than that of HBx(−) hepatocytes. Moreover, the expression of EGR1 and PPARγchanged more significantly in HBx(+) hepatocytes cultured for 12 to 24 hours in the presence of 5 mM caffeine. This limited success may be attributed to caffeine releasing the binding of HBx and PPARγand furthermore affecting the mPGES-1 expression by EGR1 in HBx(+) hepatocytes. The results indicate that caffeine could effectively reduce PGE2synthesis in HBx(+) hepatocytes by specifically blocking the PPARγ-EGR1-mPGES-1 pathway, thereby providing a new evidence of molecular biology for the hypothesis that drinking coffee is beneficial to HBV-infected patients.

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

scholarly journals Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

1999 ◽  
Vol 340 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Russell R. HOOVER ◽  
Klaus H. THOMAS ◽  
Joanna FLOROS
Keyword(s):  
Protein Complex ◽  
Promoter Activity ◽  
Nuclear Extract ◽  
Surfactant Protein ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Cis Acting ◽  
Lung Adenocarcinoma Cell Line ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Glucocorticoids have complex effects on human surfactant protein (SP) SP-A1 and SP-A2 gene expression that occur at both transcriptional and post-transcriptional levels. In the lung adenocarcinoma cell line NCI-H441, dexamethasone causes a dose-dependent decrease in total SP-A mRNA levels and inhibits SP-A gene transcription. In this study, a deletional analysis of the SP-A1 promoter was performed in order to identify cis-acting elements that mediate dexamethasone responsiveness in NCI-H441 cells. The region -32/+63 relative to the start of SP-A1 transcription mediated both basal promoter activity and dexamethasone repression of transcription. Removal of the region +18/+63 abolished dexamethasone responsiveness, indicating that sequences within this region are necessary for the inhibitory effect. Furthermore, the region -32/+63 formed a sequence-specific DNA-protein complex with NCI-H441 nuclear extract. This DNA-protein complex was induced by dexamethasone exposure and its formation was mediated partially by sequences within the region +26/+63.

scholarly journals The Molecular Biology of Vestibular Schwannomas and Its Association with Hearing Loss: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Erika Celis-Aguilar ◽  
Luis Lassaletta ◽  
Miguel Torres-Martín ◽  
F. Yuri Rodrigues ◽  
Manuel Nistal ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Molecular Biology ◽  
Cyclin D1 ◽  
Vestibular Schwannoma ◽  
Molecular Mechanisms ◽  
Platelet Derived Growth Factor ◽  
Common Symptom ◽  
The Past ◽  
New Evidence

Hearing loss is the most common symptom in patients with vestibular schwannoma (VS). In the past, compressive mechanisms caused by the tumoral mass and its growth have been regarded as the most likely causes of the hearing loss associated with VS. Interestingly, new evidence proposes molecular mechanisms as an explanation for such hearing loss. Among the molecular mechanisms proposed are methylation of TP73, negative expression of cyclin D1, expression of B7-H1, increased expression of the platelet-derived growth factor A, underexpression of PEX5L, RAD54B, and PSMAL, and overexpression of CEA. Many molecular mechanisms are involved in vestibular schwannoma development; we review some of these mechanisms with special emphasis on hearing loss associated with vestibular schwannoma.

scholarly journals Oestradiol decreases rat apolipoprotein AI transcription via promoter site B

2000 ◽  
Vol 25 (2) ◽  
pp. 207-219 ◽  
Author(s):  
AH Taylor ◽  
AE Fox-Robichaud ◽  
C Egan ◽  
J Dionne ◽  
DE Lawless ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Target Genes ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male Adult ◽  
Nuclear Extracts ◽  
Major Mode ◽  
Apo Ai

Oestrogens protect against ischaemic heart disease in the post-menopausal female by increasing serum concentrations of apolipoprotein (apo) AI and the abundance of high-density lipoprotein particles. In men and experimental male animals, the administration of oestrogen has variable effects on apo AI expression. As the major mode of oestrogen action on target genes involves regulating promoter activity and hence transcription, oestrogen is expected to alter transcription of the apo AI gene. To test this hypothesis, the effect of 17beta-oestradiol (E(2)), on rat apo AI promoter activity in male hepatoma HuH-7 cells, was tested by co-transfecting a reporter template, pAI.474.CAT containing-474 to-7 of the rat apo AI promoter and an oestrogen receptor (ER) expression vector, pCMV-ER. Transfected cells exposed to E(2) showed a dose-dependent decrease in chloramphenicol acetyltransferase (CAT)-activity, with a maximum 91+/-1.5% reduction at 1 microM E(2). Deletional analysis of the promoter localized the inhibitory effect of ER and E(2) to site B (-170 to-144) with an adjacent 5' contiguous motif, site S (-186 to-171) acting as an amplifier. HuH-7 cell nuclear extracts showed binding activities with both sites S and B, but recombinant human ER did not. Furthermore, nuclear extracts from E(2)-treated HuH-7 cells showed weaker binding activity to site B, but not to site S. In summary, the inhibitory effect of ER and E(2) on rat apo AI gene activity is mediated by a promoter element, site B. This inhibitory effect arises from a mechanism that does not involve direct ER binding to the B-element. The conclusion that E(2) inhibits apo AI transcription was confirmed in vivo. Treatment of male adult Sprague-Dawley rats with up to 200 microg E(2) for 7 days decreased apo AI protein and hepatic mRNA by 72+/-21% and 68+/-1.4% respectively. Results of 'run-on' transcription of the apo AI gene in isolated hepatic nuclei showed a 55% decrease in hormone-treated male rats. These findings suggest that E(2) exerts primarily an inhibitory effect within male hepatic nuclei.

scholarly journals The Effects of Sprint vs. Resisted Sled-Based Training; An 8-Week in-Season Randomized Control Intervention in Elite Rugby League Players

2021 ◽  
Vol 18 (17) ◽  
pp. 9241
Author(s):  
Jonathan Sinclair ◽  
Christopher James Edmundson ◽  
John Metcalfe ◽  
Lindsay Bottoms ◽  
Stephen Atkins ◽  
...  
Keyword(s):  
Training Group ◽  
Rugby League ◽  
Test Time ◽  
Training Methods ◽  
Sprint Training ◽  
Countermovement Jump ◽  
Strength And Conditioning ◽  
Control Intervention ◽  
Randomized Control ◽  
Time Point

The aim of the current study was to examine the efficacy of resisted sled-based training compared to traditional unresisted sprint training in terms of mediating improvements in speed, agility, and power during an eight-week period of in-season training in elite rugby league players. Participants were randomly separated into either resisted sled or traditional sprint-based training groups and they completed an eight-week in-season training block with training prescribed based on the group to which they were assigned. Measures of 5 m, 10 m, and 20 m sprint times in addition to countermovement jump height and 505-agility test time were measured at baseline, four-weeks and eight-weeks. For sprint-based outcomes, although both groups improved significantly, there were no statistical differences between the two training methods. However, at the eight-week time point there were significant improvements in 505-agility test (sprint group: baseline = 2.45 and eight-weeks = 2.42 s/sled group: baseline = 2.43 and eight-weeks = 2.37 s) and countermovement jump (sprint group: baseline = 39.18 and eight-weeks = 39.49 cm/sled group: baseline = 40.43 and eight-weeks = 43.07 cm) performance in the sled training group. Therefore, the findings from this investigation may be important to strength and conditioning coaches working in an elite rugby league in that resisted sled training may represent a more effective method of sprint training prescription.

scholarly journals SREBP2 mediates the modulation of intestinal NPC1L1 expression by curcumin

2011 ◽  
Vol 301 (1) ◽  
pp. G148-G155 ◽  
Author(s):  
Pradeep Kumar ◽  
Pooja Malhotra ◽  
Ke Ma ◽  
Amika Singla ◽  
Omar Hedroug ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Promoter Activity ◽  
Plasma Cholesterol ◽  
Biological Effects ◽  
Cholesterol Absorption ◽  
Inhibitory Effect ◽  
Cholesterol Homeostasis ◽  
Cholesterol Esterification ◽  
Dependent Manner ◽  
Intestinal Cholesterol Absorption

Curcumin, the major phenolic compound in the spice turmeric, exhibits numerous biological effects, including lowering plasma cholesterol and preventing diet-induced hypercholesterolemia. The mechanisms underlying the hypocholesterolemic effect of curcumin are not fully understood. In this regard, intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol transporter, the molecular target of intestinal cholesterol absorption inhibitor ezetimibe, plays an essential role in the maintenance of cholesterol homeostasis. The current studies were designed to investigate the effect of curcumin on NPC1L1 function, expression, and promoter activity in intestinal Caco-2 monolayers. NPC1L1 function was evaluated by the measurement of ezetimibe-sensitive [3H]cholesterol esterification. Relative abundance of NPC1L1 mRNA and protein was evaluated by real-time PCR and Western blotting, respectively. Luciferase assays were used to measure NPC1L1 promoter activity. Our results showed that curcumin significantly inhibited ezetimibe-sensitive cholesterol esterification in a dose-dependent manner with a maximum decrease (by 52% compared with control) occurring at 50 μM concentration. Curcumin treatment of Caco-2 monolayers also significantly decreased NPC1L1 mRNA and protein expression. Similarly, the promoter activity of the NPC1L1 gene was inhibited significantly (55%) by 50 μM curcumin. The decrease in NPC1L1 promoter activity by curcumin was associated with a reduction in the expression and the DNA-binding activity of the sterol response element-binding protein 2 (SREBP2) transcription factor. Furthermore, the overexpression of active SREBP2 protected NPC1L1 from the inhibitory effect of curcumin. Our studies demonstrate that curcumin directly modulates intestinal NPC1L1 expression via transcriptional regulation and the involvement of SREBP2 transcription factor.

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