Home About us Contact
|
Home About us Contact | ||
|
|
||
Potent Promoter (potent + promoter)
Selected AbstractsApoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytesENVIRONMENTAL TOXICOLOGY, Issue 3 2001Joanna Mankiewicz Abstract Toxic cyanobacterial blooms are an increasing problem in Poland. The production of cyanobacterial toxins and their presence in drinking and recreational waters represent a growing danger to human and animal health. This is connected with the increase of cyanobacterial biomass caused by excessive eutrophication of the water ecosystem. There is evidence that cyanobacterial hepatotoxins can act as a potent promoter of primary liver cancer. The apoptotic effect of microcystins in Polish cyanobacterial bloom samples on rat hepatocytes and human lymphocytes was observed using light and fluorescence microscopy, flow cytometry, and electrophoretic analysis. The incubation time needed to observe the first morphological apoptotic changes in hepatocytes was approximately 30 min; however, the characteristic biochemical changes in DNA were not observed even after 120 min. In lymphocyte cultures the morphological changes characteristic for apoptosis were observed after 24 h of incubation and a 48-h incubation was found to be optimal for analysis of internucleosomal DNA fragmentation, which is one of the main biochemical hallmarks of programmed cell death. These cells are an easily isolated and inexpensive material for medical diagnostics. Therefore the apoptotic changes, together with the clastogenic effect seen in lymphocyte cultures, are proposed as a future analytical method for these toxins. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 225,233, 2001 [source] Gender-dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplastyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2008Hagen S. Bachmann Abstract The G-protein G,s is involved in the physiology and pathophysiology of bone. Especially, G,s is a key regulator of interleukin-6, which is a potent promoter of aseptic loosening. We hypothesized that the common single nucleotide polymorphism GNAS1 T393C could also affect time to aseptic loosening. Caucasian patients were genotyped for the GNAS1 T393C polymorphism. Time and median time to aseptic loosening were analyzed for dependency on GNAS1 genotypes. Time and median time were not significantly associated with genotypes. Additional analysis corrected for gender revealed, that the TT genotype was associated with significantly longer time (p,=,0.048) as well as median time (p,=,0.022) to aseptic loosening in female patients. In contrast to the findings in females, male TT genotype carriers had significantly shorter time (p,=,0.018) and median time (p,=,0.023) to aseptic loosening. Compared with TT genotype carriers heterozygous patients had a 6.25-fold lower risk with a hazard ratio of 0.160 (p,=,0.016) and male patients carrying the CC genotype had an 11-fold lower risk with a hazard ratio of 0.088 (p,=,0.006) in multivariate analysis. The present study suggests a significant gender-dependent role of the T393C polymorphism in aseptic loosening. The apparently contradictory results in women and men and the finding that the GNAS1 T393C genotype is an independent factor for time to aseptic loosening in male patients assigned this polymorphism as an interesting target for further investigations in bone diseases. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] A novel synthetic mammalian promoter derived from an internal ribosome entry siteBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2006Shizuka Hartenbach Abstract Introduction of specific mutations into a synthetic internal ribosome entry site (IRESGTX) derived from the GTX homeodomain protein revealed additional transcriptional activity. This novel synthetic PGTX promoter exhibited consensus core promoter modules such as the initiator (Inr) and the partial downstream promoter elements (DPE) and mediated high-level expression of a variety of transgenes including the human vascular endothelial growth factor 121 (VEGF121), the human placental secreted alkaline phosphatase (SEAP), and the Bacillus stearothermophilus -derived secreted ,-amylase (SAMY) in Chinese hamster ovary cells (CHO-K1) and a variety of other mammalian and human cell lines. The spacing between Inr and DPE modules was found to be critical for promoter performance since introduction of a single nucleotide (resulting in PGTX2) doubled the SEAP expression levels in CHO-K1. PGTX2 reached near 70% of PSV40 -driven expression levels and outperformed constitutive phosphoglycerate kinase (PPGK) and human ubiquitin C (PhUBC) promoters in CHO-K1. Also, PGTX2 was successfully engineered for macrolide-inducible transgene expression. Owing to its size of only 182 bp, PGTX2 is one of the smallest eukaryotic promoters. Although PGTX2 was found to be a potent promoter, it retained its IRESGTX -specific translation-initiation capacity. Synthetic DNAs, which combine multiple activities in a most compact sequence format may foster advances in therapeutic engineering of mammalian cells. © 2006 Wiley Periodicals, Inc. [source] 3T3-L1 adipocyte apoptosis induced by thiazolidinediones is peroxisome proliferator-activated receptor-,-dependent and mediated by the caspase-3-dependent apoptotic pathwayFEBS JOURNAL, Issue 3 2010Yuanyuan Xiao Although thiazolidinediones (TZDs) are potent promoters of adipogenesis in the preadipocyte, they induce apoptosis in several other cell types, such as cancer cells, endothelial cells and T-lymphocytes. In this study, we investigated the proapoptotic effect of TZDs in mature 3T3-L1 adipocytes, which express high levels of the peroxisome proliferator-activated receptor-, (PPAR,) protein. Apoptosis was induced in mature 3T3-L1 adipocytes by treatment with troglitazone, pioglitazone or prostaglandin J2, and could be blocked by the PPAR, antagonist GW9662. Treatment with PPAR, agonists also decreased Akt-1 protein and phosphorylation levels without affecting phosphoinositide 3-kinase and PTEN. Further analysis indicated that in troglitazone-treated 3T3-L1 adipocytes, Bad phosphorylation and Bcl-2 protein levels were reduced, and Bax translocation to the mitochondria was increased. Subsequently, cytochrome c release and caspase-3 cleavage were observed. TZD-induced adipocyte apoptosis could be blocked by the caspase-3 inhibitor Ac-DEVD-CHO or by overexpression of Bcl2. In cultured rat primary adipocytes, similar apoptosis-inducing effects of troglitazone were also observed. Thus, TZDs promote apoptosis in adipocytes through a PPAR,-dependent pathway. This apoptosis is mediated by the inhibition of Akt-1, which decreases Bad phosphorylation and activates the mitochondrial apoptotic pathway. [source] Cigarette smoke condensate induces nuclear factor kappa-b activity and proangiogenic growth factors in aerodigestive cells,THE LARYNGOSCOPE, Issue 8 2010Joseph Rohrer MD Abstract Objectives/Hypothesis: Aerodigestive cancer risk of both lung and head and neck cancers has been linked to the genotoxic effects of tobacco use. These effects include upregulation of nuclear factor kappa-B (NF,B) and its downstream products associated with both lung and head and neck cancer malignant progression. Study Design: Bench Research. Methods: In the present study we examined the effects of cigarette smoke condensate on functional activation of NF,B in human papillomavirus (HPV)-transformed oral cavity cells (HOK 16B cells) and transformed bronchial epithelium (Beas2B cells) using the head and neck squamous cancer cell line, UMSCC 38, as a comparison. Luciferase reporter gene assays with two types of transiently transfected NF,B reporter genes were employed and downstream NF,B-dependent products, interleukin-6, interleukin-8, and vascular endothelial growth factor, were assayed by enzyme-linked immunosorbent assay. Results: All cell lines were able to dose dependently activate NF,B reporter genes after exposure to cigarette smoke condensate (P < .05). However, the HPV premalignant, transformed cell line had a much more robust NF,B response (3.45-fold) versus the squamous cancer cell line (1.62-fold) and SV40 transformed Beas2B (1.83). Both NF,B reporter genes had similar response curves. Conclusions: This study demonstrates cigarette smoke products might be more potent promoters of an NF,B-dependent progression from HPV+ premalignancy to cancer rather than after tumors are established. Future studies should focus on abrogating NF,B increases during malignant progression and premalignancy. This might be even more relevant in the HPV+ patient with premalignancy. Laryngoscope, 2010 [source] | ||||||||||