Vitamin A excess alters membrane flow in rat liver

Pulse-chase methodology with [35S]methionine as label was employed to determine flow kinetics through the endoplasmic reticulum-Golgi apparatus-(lysosome-) secretory vesicle-plasma membrane export route in livers of animals receiving vitamin A excess by gavage. Overall fraction composition determined by morphometry and by analyses of marker enzymes was unchanged by vitamin administration. The vitamin modified the pattern of flow of proteins through the Golgi apparatus to the cell surface and to lysosomes. Altered flux was evidenced by a markedly reduced rate of labeling of lysosomes and a slightly increased rate of labeling of both total membrane proteins of the plasma membrane and of a specific membrane glycoprotein GP80. Also reduced was overall labeling of the Golgi apparatus. Differences in the rate or routes of trafficking of glycoproteins through the Golgi apparatus together with altered opportunities for processing might account for some of the alterations in glycoconjugate glycosylation associated with excess vitamin A administration.     

Vitamin A deficiency induces prooxidant environment and inflammation in rat aorta

We evaluated whether nutritional vitamin A deficiency generates oxidative stress and inflammation in aorta. Wistar male rats (21 days old) were given free access to a control (8 mg retinol as retinyl palmitate/kg) or a vitamin A- deficient diet for three months. One group of deficient animals was fed with the control diet fifteen days before sacrifice. Thiobarbituric acid-reactive substances (TBARS) and nitrite concentration where both analyzed in serum and aorta. Aorta Copper-Zinc Superoxide dismutase (CuZnSOD), Glutathion peroxidase (GPx) and Catalase (CAT) activities were measured. In addition, binding activity of the nuclear factor- kB (NF-kB), inducible and endothelial Nitric Oxide synthase (iNOS and eNOS, respectively) and Ciclooxygenase-2 (COX-2) expressions were determinated in aorta. Rats fed the vitamin A- deficient diet were characterized by sub-clinical plasma retinol concentration and showed increased serum and aorta concentrations of TBARS compared to controls. Lower than control activities of CuZnSOD, GPx, and CAT were observed in aorta of the vitamin A- deficient group. The binding activity of NF- kB was higher in vitamin A- deficient animals than controls. In addition, NO production evaluated as nitrite concentration increased in aorta and serum, associated with a higher expression of iNOS, eNOS and COX-2 in aorta of vitamin A-deficient rats. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted the changes observed in TBARS level, CuZnSOD and GPx activities, nitrite concentration and also, iNOS, eNOS and COX-2 expression. Prooxidant environment and inflammation are induced by vitamin A deficiency in rat aorta.     

Vitamin A promotes DNA synthesis and mitosis in blastemas of Triturus alpestris

Vitamin A palmitate orally administered to young, post-metamorphic Triturus alpestris (Amphibia-Urodela), for 4 and 7 days after bilateral forelimb amputation at the middle of the zeugopodium, enhanced the mean DNA content of the blastema cells. Moreover, the number of cells in mitosis was nearly twice as high in vitamin A treated animals than in control ones.     

Enhancing isoprenoid synthesis in Yarrowia lipolytica by expressing the isopentenol utilization pathway and modulating intracellular hydrophobicity

The abundant supply of biosynthetic precursors and product compatibility with the intracellular environment play important roles for microbial isoprenoid production. In this study, we tailor to both of these requirements by introducing the two-step isopentenol utilization pathway (IUP) to augment the native pathway in the oleaginous yeast Yarrowia lipolytica. With shortcut access to the common isoprenoid precursor, isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP), IUP is capable of elevating IPP + DMAPP levels by 15.7-fold compared to the mevalonate pathway alone. The increase in IPP + DMAPP levels can directly lead to better isoprenoid synthesis, which is illustrated using lycopene as a model compound. Moreover, we also demonstrate that higher lipid contents in the cells correlate with improved intracellular lycopene production, suggesting the importance of having a substantial hydrophobic environment to sequester isoprenoids. Combining these strategies with further genetic and fermentation optimizations, we achieved a final lycopene titer of 4.2 g/L. Overall, these strategies hold great potential for strengthening the synthesis of long-chain isoprenoids and fat-soluble natural products in microbes.     

Vitamin A-deficiency and thyrotropin secretion in the rat.

Basal serum TSH concentrations and TRH-induced TSH response were studied in control and in vitamin A-deficient rats at different times between the fifth week on diet (when growth of deficient animals was still normal) and the beginning of the weight plateau (as soon as growth of deficient animals had stopped). In deficient rats the TSH values were always lower than in the control rats. TRH injections (50 ng/100 g b.w.) in anaesthetized animals (amobarbital 1 mg/100 g b.w.) resulted in an approximately 12-fold increase in serum TSH levels within 6 minutes. The TSH levels remained elevated for at least 15 minutes and were similar in control and deficient rats. We hypothesize that the lower basal serum TSH concentrations are the result of a feedback mechanism triggered by an increase of serum free thyroxine (FT4) and free triiodothyronine (FT3).