Search results for "Mevalonic Acid"
showing 3 items of 13 documents
Bisphosphonates and atherosclerosis: why?
2005
The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget’s disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms fo…
Targeting the mevalonate pathway for improved anticancer therapy.
2009
The mevalonate pathway is important for the generation of isoprene moieties thereby providing the basis for the biosynthesis of molecules required for maintaining membrane integrity, steroid production and cell respiration. Additionally, isoprene precursors are indispensable for the prenylation of regulatory proteins such as Ras and Ras-homologous (Rho) GTPases. These low molecular GTP-binding proteins play key roles in numerous signal transduction pathways stimulated upon activation of cell surface receptors by ligand binding. Thus, Ras/Rho proteins eventually regulate cell proliferation, tumor progression and cell death induced by anticancer therapeutics. Lipid modification of Ras/Rho pro…
Inhibition of small G proteins of the Rho family by statins orClostridium difficiletoxin B enhances cytokine-mediated induction of NO synthase II
2000
In order to investigate the involvement of Ras and/or Rho proteins in the induction of the inducible isoform of nitric oxide synthase (NOS II) we used HMG-CoA reductase inhibitors (statins) and Clostridium difficile toxin B (TcdB) as pharmacological tools. Statins indirectly inhibit small G proteins by preventing their essential farnesylation (Ras) and/or geranylgeranylation (Rho). In contrast, TcdB is a glucosyltransferase and inactivates Rho-proteins directly. Human A549/8- and DLD-1 cells as well as murine 3T3 fibroblasts were preincubated for 18 h with statins (1–100 μM) or TcdB (0.01–10 ng ml−1). Then NOS II expression was induced by cytokines. NOS II mRNA was measured after 4–8 h by R…