The peak bone mass and the rate of bone loss are in part genetically determined. It has been suggested that bone mineral density (BMD) may be related to allelic variation in the apolipoprotein E (ApoE) gene locus. ApoE is important in the receptor-mediated clearance of chylomicron particles from the plasma, Apo E4 having the highest and Apo E2 the lowest receptor affinity. Chylomicrons are the main carrier of vitamin K in the plasma; vitamin K plays an important role in the carboxylation of osteocalcin. We have tested the hypothesis that persons with E4 variant would have lower BMD and increased bone turnover than those with E2 variant. A total of 18 ApoE 2/2 and ApoE 4/4 homozygotes were selected from 873 patients who were examined for the ApoE genotype. BMD in lumbar vertebral, femoral neck and distal forearm was measured and plasma concentrations of osteocalcin and C-terminal fragments of collagen (CTx) were determined. BMD values (expressed as T-score) at the three specified sites were -0.12± 1.72, -0.52± 1.32 and -0.52± 0.81 in ApoE 2/2 group and -0.24± 1.22, 0.00± 0.84 and -0.17± 1.07 in the ApoE 4/4 group. Plasma osteocalcin and CTx were within normal limits in both groups. In conclusion, we did not observe any association of ApoE genotype with BMD and biochemical markers of bone metabolism in ApoE 2/2 and ApoE 4/4 homozygotes., T. Štulc, R. Češka, A. Hořínek, J. Štěpán., and Obsahuje bibliografii
Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. This study is focused on addressing the mutual relationship and early signals of these mechanisms in the D-galactosamine and lipopolysaccharide (D-GalN/LPS) hepatotoxicity model, with the help of standard liver function and biochemistry tests, histology, and measurement of gene expression by RT-PCR. Intraperitoneal injection of 400 mg/kg D-GalN and 50 μg/kg LPS was able to induce hepatotoxicity in rats, as evidenced by significant increases in liver enzymes (ALT, AST) and raised bilirubin levels in plasma. Heme oxygenase-1 and nitric oxide synthase-2 gene expressions were significantly increa sed, along with levels of their products, bilirubin and nitrite. Th e gene expression of glutathione peroxidase 1 remained unchanged, whereas a decrease in superoxide dismutase 1 gene expression was noted. Furthermore, the significant increase in the gene expression of apoptotic genes Bid, Bax and caspase-3 indicate early activation of apoptotic pathways, which was confirmed by histological evaluation. In contrast, the measured caspase-3 activity remained unchanged. Overall, the results have revealed differential oxidative stress and apoptotic responses, which deserves further investigations in this hepatotoxicity model., N. Lekić ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Apolipoprotein E (apoE) is a polymorphic protein which occurs in three common isoforms and more than 25 rare variants. Some of the rare apoE variants have been implicated in a dominant mode of inheritance of familial dysbetalipoproteinemia (FD). We have identified three unrelated apoE 2*(Arg136®Cys) carriers with FD. This finding supports the notion that although apoE 2*(Arg136®Cys) mutation is perhaps not sufficient to cause FD itself, the presence of other genetic and/or environmental factors can lead to the phenotypic expression of the disease in the carriers., M. Vrablík, A. Hořínek, R. Češka, T. Štulc, T. Kvasnička., and Obsahuje bibliografii
Apolipoprotein (apo) B-100 is a key protein compound of plasma lipid metabolism. This protein, as a sole component of LDL particles, to a great extent controls the homeostasis of LDL cholesterol in the plasma. Therefore, this protein and its structural variants play an important role in development of hyperlipidemia and atherosclerosis. Intensive research into the structure and biological functions of apoB-100 has led to identification of its complete structure as well as the responsible binding sites. With the development of the methods of molecular biology, some structural variants of the apoB-100 protein that directly affect its binding properties have been described. These are mutations leading to amino acid substitution at positions 3500 (R3500Q and R3500W) and 3531 (R3531C) that have been shown to decrease the binding affinity of apoB-100 in vitro. However, only the former mutations have been unequivocally demonstrated to cause hyperlipidemia in vivo. This minireview is aimed to discuss the impact of apoB-100 and its structural variants on plasma lipid metabolism and development of hyperlipidemia., M. Vrablík, R. Češka, A. Hořínek., and Obsahuje bibliografii