Cholesterol and mevalonic acid modulation in cell metabolism and multiplication.

摘要: Cholesterol in animals is a major structural component of cell membranes. It may therefore play functional role the modulation osmolarity, process pinocytosis and activities membrane-associated proteins such as ionic pumps, immune responses, etc. A relationship exists between cell-growth processes cholesterol biosynthetic pathway. The needed for new membranes be derived either from endogenous synthesis or exogenous sources, principally plasma low-density-lipoproteins (LDL) which enter cells by receptor-mediated endocytosis. Both these pathways are enhanced rapidly growing cells. Conversely, if inhibited no available, growth blocked. 3-hydroxy-3-methylglutaryl CoA (HMGCoA) reductase (the rate-limiting reaction biosynthesis) enzyme catalyzes conversion HMGCoA to mevalonic acid. has been suggested that mevalonate an important proliferation. All need at least two products synthesized order proliferate, only one yet identified cholesterol. Other melavonate-derived potential candidates cell-cycle cell-survival include dolichols ubiquinone side chains, isopentenyladenosine derivatives, Furthermore, it recently shown membrane association appears function mevalonate-derive modifications several cellular G proteins, those coded oncogenes (ras proteins) lamins (nuclear proteins). In recent years development cholesterol-synthesis-inhibiting drugs, lowering levels mainly centred on control activity (vastatins). However, because acid precursor numerous metabolites, any reduction potentiate pleiotropic effects. Vastatins now, therefore, receiving increased attention pharmacological tools abnormal pathological situations, i.e. tumours vascular smooth muscle proliferation under atherogenic conditions. our laboratories, we have demonstrated simvastatin can prevent arterial myocyte both vivo vitro. Simvastatin also inhibit vitro rate human glioma growth, since shows strong synergistic inhibitory effect when used with anticancer agents Carmustine beta-interferon. simvastatin-induced inhibition synergy observed drugs completely reversed incubating mevalonate. This due its specific intracellular synthesis.