Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory activation of the endothelium by Chlamydophila pneumoniae infection has been implicated in the development of chronic vascular lesions and coronary heart disease by seroepidemiological and animal studies. We tested the hypothesis that C. pneumoniae induced inflammatory gene expression is regulated by Rho-GTPase-related histone modifications. C. pneumoniae infection induced the liberation of proinflammatory interleukin-6, interleukin-8, granulocyte colony-stimulating factor, macrophage inflammatory protein-1beta, granulocyte/macrophage colony-stimulating factor, and interferon-gamma by human endothelial cells. Cytokine secretion was reduced by simvastatin and the specific Rac1 inhibitor NSC23766 but was synergistically enhanced by inhibitors of histone deacetylases trichostatin A and suberoylanilide hydroxamic acid. Infection of endothelial cells with viable C. pneumoniae, but not exposure to heat-inactivated C. pneumoniae or infection with C. trachomatis, induced acetylation of histone H4 and phosphorylation and acetylation of histone H3. Pretreatment of C. pneumoniae-infected cells with simvastatin or NSC23766 reduced global histone modifications as well as specific modifications at the il8 gene promoter, as shown by chromatin immunoprecipitation. Reduced recruitment of nuclear factor kappaB p65/RelA as well as of RNA polymerase II was observed in statin-treated cells. Taken together, Rac1-mediated histone modifications seem to play an important role in C. pneumoniae-induced cytokine production by human endothelial cells.
 ...
PMID:Simvastatin reduces Chlamydophila pneumoniae-mediated histone modifications and gene expression in cultured human endothelial cells. 1843 97

MicroRNAs represent a class of small (19-25 nucleotides) single-strand pieces of RNA, that are non-coding ones. They are synthesized by RNA polymerase II from transcripts which fold back on themselves. They mostly act as gene regulatory agents, that pair with complementary sequences on mRNA and produce silencing complexes, which in turn suppress coding genes at a post-transcriptional level. There is now evidence that microRNAs may affect insulin secretion or insulin action, as they can alter pancreatic beta cells development, insulin production, as well as insulin signalling. Any molecular disorder that affects these pathways can deteriorate insulin resistance and lead to type 2 diabetes mellitus (T2DM) onset. Furthermore, the expression of several microRNAs is up- or down-regulated in the presence of diabetic microvascular complications (i.e. peripheral neuropathy, nephropathy, retinopathy, foot ulcers), as well as in patients with coronary heart disease, stroke, and peripheral artery disease. However, more evidence is needed, specifically regarding T2DM patients, to establish the use of such microRNAs as diagnostical biomarkers or therapeutic targets in daily practice.
 ...
PMID:The role of microRNAs in the development of type 2 diabetes complications. 3313 53