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Biomedical subjects

I Zelikovic

Publications and source records attributed to I Zelikovic.

45 records · Page 3Linked to original sources

Studies on renal adaptation to altered dietary amino acid intake: tissue taurine responses in nursing and adult rats.

This study examines the effect of a low sulfur amino acid diet (LTD) and a high taurine diet (HTD), compared with a normal diet, on the plasma, urine, muscle, brain and renal cortex levels of taurine in immature and adult rats. Milk taurine from lactating dams reflected the taurine content of the diet, being low in LTD-fed and high in HTD-fed animals. Nursing pups (7, 14 and 21 d old) often had plasma, urine and tissue--renal cortex, heart, skeletal muscle--levels of taurine related to dietary exposure, a situation also found in adult animals. These diets did not influence the urinary excretion of the sulfur-containing alpha-amino acids methionine and cystine but a sulfur aminoaciduria of immaturity was evident. By contrast, the content of taurine in brain was constant regardless of dietary intake of sulfur amino acids. An age-related decline in brain taurine content was found--as noted by others--but this too was influenced by diet. This dual finding of brain taurine constancy despite wide differences in sulfur amino acid intake and changes in the renal handling of taurine as influenced by diet suggest that the renal adaptive response serves to maintain the stability of brain taurine content.

Adaptation, Physiological↗

Membrane fluidity and phospholipid composition in relation to sulfur amino acid intake in brush border membranes of rat kidney.

The transport of ions and solutes across biological membranes may relate to changes in the lipid microenvironment of the membrane which could alter the activity or configuration of transport sites. Changes in the sulfur amino acid content of diets fed to young rats results in an increase in Na+-taurine symport in brush border membranes isolated from animals fed a low sulfur amino acid diet and a reduction in symport after a high taurine diet in comparison to uptake by membranes from normally fed animals ("the renal adaptive response"). We explored the possibility that diet-induced changes in brush border membrane symport relate to altered membrane fluidity and phospholipid composition in response to diet. An Arrhenius plot of initial rate (15 s) taurine uptake in breakpoint at 22 degrees C, but no change in relation to dietary alteration. Fluorescence polarization data employing the probe 1-6-diphenyl-1,3,5-hexatriene best fits a two-phase linear model employing a computer model fitting program. Dietary manipulations did not change the breakpoint upper segment slope or lower segment slope after incubating fresh membranes with DPH over the temperature range 4-56 degrees C. No change was evident in membrane phospholipid composition in relation to diet. This study indicates that the changes in initial rate Na+-taurine symport in relation to diet are less likely to be due to changes in the configuration of the transporter from an alteration of the lipid microenvironment of the membrane.

Amino Acids, Sulfur↗

Hepatorenal syndrome in neonates.

Two neonates with hepatorenal syndrome are described. In both infants, the syndrome was precipitated by ascitic aspiration. The main pathogenetic mechanisms are reviewed, and a plea is made to use caution when considering therapeutic manipulations in infants with liver disease in order to avoid the development of the hepatorenal syndrome.

Acute Kidney Injury↗

The taurine transporter: mechanisms of regulation.

Taurine transport undergoes an adaptive response to changes in taurine availability. Unlike most amino acids, taurine is not metabolized or incorporated into protein but remains free in the intracellular water. Most amino acids are reabsorbed at rates of 98-99%, but reabsorption of taurine may range from 40% to 99.5%. Factors that influence taurine accumulation include ionic environment, electrochemical charge, and post-translational and transcriptional factors. Among these are protein kinase C (PKC) activation and transactivation or repression by proto-oncogenes such as WT1, c-Jun, c-Myb and p53. Renal adaptive regulation of the taurine transporter (TauT) was studied in vivo and in vitro. Site-directed mutagenesis and the oocyte expression system were used to study post-translational regulation of the TauT by PKC. Reporter genes and Northern and Western blots were used to study transcriptional regulation of the taurine transporter gene (TauT). We demonstrated that (i) the body pool of taurine is controlled through renal adaptive regulation of TauT in response to taurine availability; (ii) ionic environment, electrochemical charge, pH, and developmental ontogeny influence renal taurine accumulation; (iii) the fourth segment of TauT is involved in the gating of taurine across the cell membrane, which is controlled by PKC phosphorylation of serine 322 at the post-translational level; (iv) expression of TauT is repressed by the p53 tumour suppressor gene and is transactivated by proto-oncogenes such as WT1, c-Jun, and c-Myb; and (v) over-expression of TauT protects renal cells from cisplatin-induced nephrotoxicity.

Adult↗