0000000000846688
AUTHOR
Santiago Vernia
Involvement of Peroxynitrite on the Early Loss of P450 in Short-Term Hepatocyte Cultures
The biological chemistry of nitric oxide (NO) in the oxygenated cellular environment is extremely complex. It involves the direct interaction of NO with specific biomolecules and the so-called indirect effects, due to secondary more potent oxidant species derived from NO which are also able to react with DNA, lipids, thiols and transition metals (Wink et al. 1996; Nathan, 1992). In addition to its regulatory role as a signalling molecule (Nathan, 1992; Moncada and Palmer, 1991) it has become evident that NO (or NO-derived species) is a critical factor involved in various toxicological mechanisms (Wink et al. 1996; Wang et al. 1998; Estevez et al. 1999; Wink et al. 1999). Some controversy ex…
Differential sensitivity of rat hepatocyte CYP isoforms to self-generated nitric oxide.
AbstractEarly loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study investigates the influence of endogenously generated NO (or NO-derived species) on the relative expression of cytochrome P450 (CYP) isoforms in rat hepatocytes. Our results support the view that loss of P450 holoenzyme in culture is the ultimate consequence of a NO driven process, activated during the common hepatocyte isolation procedure, that leads to an accelerated and selective degradation of specific CYP apoproteins. Under conditions in which NO and peroxynitrite formation is operative, changes in the level of specific CYP isoforms result in a significant alter…
A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia.
Autosomal dominant hypercholesterolemia (ADH) is a genetic disorder characterized by increased low-density lipoprotein (LDL)-cholesterol levels, leading to high risk of premature cardiovascular disease. More than 900 mutations in LDL receptor, six in APOB and 10 in PCSK9 have been identified as a cause of the disease in different populations. All known mutations in PCSK9 causing hypercholesterolemia produce an increase in the enzymatic activity of this protease. Up to now, there are data about the implication of PCSK9 in ADH in a low number of populations, not including a Spanish population.The objective of the study was to study the prevalence of PCSK9 mutations in ADH Spanish population.W…