Search results for "Transcription"
showing 10 items of 2278 documents
Nitric oxide synthase: expression and expressional control of the three isoforms.
1995
Three isozymes of nitric oxide synthase (NOS) have been identified. Their cDNA- and protein structures as well as their genomic DNA structures have been described. NOS I (ncNOS, originally discovered in neurons) and NOS III (ecNOS, originally discovered in endothelial cells) are low output, Ca(2+)-activated enzymes whose physiological function is signal transduction. NOS II (iNOS, originally discovered in cytokine-induced macrophages) is a high output enzyme which produces toxic amounts of NO that represent an important component of the antimicrobial, antiparasitic and antineoplastic activity of these cells. Depending on the species, NOS II activity is largely (human) or completely (mouse a…
The immunosuppressive activity of artemisinin‐type drugs towards inflammatory and autoimmune diseases
2021
The sesquiterpene lactone artemisinin from Artemisia annua L. is well established for malaria therapy, but its bioactivity spectrum is much broader. In this review, we give a comprehensive and timely overview of the literature regarding the immunosuppressive activity of artemisinin-type compounds toward inflammatory and autoimmune diseases. Numerous receptor-coupled signaling pathways are inhibited by artemisinins, including the receptors for interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), β3-integrin, or RANKL, toll-like receptors and growth factor receptors. Among the receptor-coupled signal transducers are extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinas…
Effects of triterpenes on the immune system.
2010
Ethnopharmacological relevance: Triterpenes, which comprise a broad chemical group of active principles, are implicated in the mechanisms of action and pharmacological effects of many medicinal plants used in folk medicine against diseases in which the immune system is implicated. They have been described as anti-inflammatory, antiviral, antimicrobial, and antitumoral agents, as well as being immunomodulator compounds. Several of them are implicated in the resolution of immune diseases, although their effects have not always been clearly correlated. Aim of the review: The aim of this review is to compile relevant data on the mechanisms of action of triterpenes isolated from active ethnomedi…
Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches.
2014
Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria. Cells respond to different physiologic, metabolic, and pathologic changes by regulating this organelle with high morphological and functional adaptability. A considerable number of proteins, transcription factors, upstream regulatory proteins and secondary mechanisms are involved in MB and the stabilization of new mitochondrial DNA. These MB activators and regulators, including the main participating proteins (e.g. PGC-1α and mtTFA), are candidates for therapeutic intervention in diverse diseases, like neurodegenerative disorders, metabolic syndrome, sarcopenia, cardiac pathophysiolo…
The multiplicity of Argonaute complexes in mammalian cells
2022
Argonautes (AGOs) are a highly conserved family of proteins found in most Eukaryotes, and involved in mechanisms of gene regulation, both at the transcriptional and post-transcriptional level. Among other functions, AGO proteins associate with microRNAs to mediate the post-transcriptional repression of protein-coding genes. In this process, AGOs associate with members of the trinucleotide repeat containing 6 protein (TNRC6) protein family to form the core of the RNA-induced silencing complex (RISC), the effector machinery that mediates microRNA function. However, the description of the exact composition of the RISC has been a challenging task due to the fact the AGO's interactome is dynamic…
Transcriptional regulation and expression of CYP3A4 in hepatocytes.
2007
CYP3A4 is the most abundantly expressed drug-metabolizing P450 enzyme in human liver and contributes to the metabolism of a large number of drugs in use today. CYP3A4 is constitutively expressed in adult hepatocytes but it can also be transcriptionally induced by a variety of structurally diverse xenochemicals. CYP3A4 strongly contributes to the important variability in the therapeutic and toxic effects of drugs owing to the major role it plays in xenobiotic metabolism and the large intra- and inter-individual variability to which it is subjected. The functional examination of up to 13 kb of the CYP3A4 5'-flanking region has revealed that the regulation of this gene is a complex issue, with…
321. Sea Urchin sns Chromatin Insulator Prevents Silencing and Positional Effect Variegation of Oncoretroviral Vectors Transgene Expression in Murine…
2006
Silencing and position effect are considered significant obstacles to obtain a consistent level of transgene expression in viral gene therapy. Furthermore recent studies had shown that retroviruses tend to land on active genes with the potential consequence of insertional mutagenesis. The inclusion of elements, such as chromatin insulators, capable to insulate a gene from the surrounding chromatin effects at the integration site should improve both efficacy and safety of gene therapy vectors. We have previously characterized a 265 bp insulator element, termed sns, localized at the 3’ end of the early histone H2A gene of the sea urchin Paracentrotus lividus. This sequence contains three cis-…
A Symphytum officinale Root Extract Exerts Anti-inflammatory Properties by Affecting Two Distinct Steps of NF-κB Signaling
2019
Symphytum officinale, commonly known as comfrey, constitutes a traditional medicinal plant with a long-standing therapeutic history, and preparations thereof have been widely used for the treatment of painful muscle and joint complaints, wound and bone healing, and inflammation. Today, its topical use is based on its analgesic and anti-inflammatory effects, which have been substantiated by modern clinical trials. However, the molecular basis of its action remained elusive. Here, we show that a hydroalcoholic extract of comfrey root impairs the development of a pro-inflammatory scenario in primary human endothelial cells in a dose-dependent manner. The extract, and especially its mucilage-de…
Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor-αby inhibiting nuclear factor-κB activation
2003
The marine product cacospongionolide B, a sesterterpene isolated from the Mediterranean sponge Fasciospongia cavernosa, is an inhibitor of secretory phospholipase A2 with anti-inflammatory properties. In this work, we have studied the mechanism of action of this compound in the inflammatory response induced by zymosan in primary cells and in the mouse air pouch. In mouse peritoneal macrophages, cacospongionolide B was able to downregulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), resulting in decreased production of NO and prostaglandin E2 (PGE2). This compound also reduced tumour necrosis factor-α (TNF-α) mRNA expression and TNF-α levels. Cacosp…
Structure of the phenylalanine hydroxylase gene in Drosophila melanogaster and evidence of alternative promoter usage.
1996
The complete Drosophila melanogaster phenylalanine hydroxylase gene isolated from a genomic library was sequenced. Gene structure consisted of five exons covering a region of around 3 kb. Position of introns in the C-terminal domain was conserved with mammalian aromatic amino acid hydroxylase genes. Putative promoter sequences in the 5'UTR and intron 1 were identified. A novel transcript was detected differing from that previously reported by the inclusion of a part of the intron 1 sequence. It could be produced using an alternative promoter. The deduced open reading frame would code a protein with a small difference at the N-terminus. Expression of the alternative transcripts was examined …