1 |
Inflammation affects ontogeny of L-carnitine hmeostasis mechanisms in the developing rat2013 December 1900 (has links)
ABSTRACT
This thesis research involved investigations into the effects of inflammation on maturation of L-carnitine homeostasis in developing rat neonates. The overall hypothesis was an inflammatory stimulus will alter the ontogeny of L-carnitine homeostasis pathways and this depends upon when the inflammatory stimulus occurs in postnatal development. The objective was to investigate the potential effect of inflammation on carnitine transporter expression in different age groups of neonates and evaluation of effect of inflammation on ontogeny and activity of enzymes involved in carnitine biosynthesis and whether this differs depending upon when in postnatal development the inflammatory stimulus occurs.
Rat pups at postnatal day 3, 7, and 14 received an intraperitoneal injection of lipopolysaccharide (LPS) at a dose known to cause a febrile reaction in rat neonates. L-Carnitine homeostasis pathways underwent significant ontogenesis during postnatal development in the rat. LPS administration caused a significant decrease in free L-carnitine levels in serum and heart tissue and a decrease in mRNA expression levels of the high affinity carnitine transporter, Octn2, in kidney, heart and intestine at all postnatal ages. Furthermore, significant decreases in mRNA expression levels of key enzymes involved in carnitine biosynthesis was observed, while an increase in carnitine palmitoyltransferase mRNA levels were observed at all postnatal ages. Reductions in butyrobetaine hydroxylase mRNA expression were paralleled by reductions in enzyme activity only at postnatal day 3 and 7. Heart creatine phosphate levels were deceased significantly in LPS treated groups in all postnatal ages; however, ADP and ATP levels were unaffected. Collectively, this research provided experimental evidence for a significant effect of inflammation on changes in L-carnitine homeostasis maturation in early neonatal stages. The maturation of physiological processes may be altered by external factors in early postnatal life.
|
2 |
Expression von Aufnahme-Transportern für Zytostatika in Mamma- und Prostatakarzinom-Zellen und ihre Interaktion mit Zytostatika / Expression of uptake-transportproteins for antineoplastic drugs in cell lines from mamma and prostate carcinomaMüller, Judith 12 June 2017 (has links)
No description available.
|
3 |
Studies of the expression and characterization of various transport systems at RBE4 cells, an in vitro model of the blood-brain barrier / Studien zur Expression und Charakterisierung verschiedener Transport Systeme an RBE4 Zellen, einem in vitro Modell der Blut-Hirn SchrankeFriedrich, Anne 05 July 2003 (has links) (PDF)
The purpose of this study was the investigation of several transport systems expressed at the BBB. The identification and functional characterization of such transport systems is essential to provide a basis for strategies to regulate drug disposition into the brain. Immortalized rat brain endothelial cells (RBE4 cells) have been used in this study as an in vitro model of the BBB. The present study has shown that the RBE4 cells are a suitable model of the BBB for transporter studies. These cells do express the amino acid transport systems L and y+, which are known to be present at the BBB. The uptake of L-tryptophan, a neutral amino acid transported by system L, exhibited a half saturation constant (Kt) of 31 µM and a maximal velocity rate (Vmax) of about 1 nmol/mg/min in RBE4 cells. The kinetic constants of the L-arginine uptake, representing system y+ transport activity, into RBE4 cells were determined with a Kt value of about 55 µM and a Vmax of 0.56 nmol/mg/min. Furthermore the expression of two sodium dependent transporters, the 5-HT transporter (SERT) and the organic cation/carnitine transporter OCTN2, was shown at the RBE4 cells. Uptake studies with radiolabeled 5-HT exhibited a saturable, sodium dependent transport at RBE4 cells with a Kt value of about 0.40 µM and a Vmax of about 52 fmol/mg/min. L-carnitine and TEA (tetraethylammonium) are known to be transported by the OCTN2 transporter. The uptake of L-carnitine into RBE4 cells was shown to be sodium dependent and saturable with a Kt value of 54 µM and a maximal velocity of about 3.6 pmol/mg/min. In contrast, the organic cation TEA follows a sodium independent uptake mechanism at RBE4 cells. Also a sodium independent choline uptake into the cells was discovered but the molecular identity remained unknown. This saturable choline transport exhibited a Kt value of about 22 µM and a maximal velocity of about 52 pmol/mg/min.
|
4 |
Studies of the expression and characterization of various transport systems at RBE4 cells, an in vitro model of the blood-brain barrierFriedrich, Anne 08 November 2002 (has links)
The purpose of this study was the investigation of several transport systems expressed at the BBB. The identification and functional characterization of such transport systems is essential to provide a basis for strategies to regulate drug disposition into the brain. Immortalized rat brain endothelial cells (RBE4 cells) have been used in this study as an in vitro model of the BBB. The present study has shown that the RBE4 cells are a suitable model of the BBB for transporter studies. These cells do express the amino acid transport systems L and y+, which are known to be present at the BBB. The uptake of L-tryptophan, a neutral amino acid transported by system L, exhibited a half saturation constant (Kt) of 31 µM and a maximal velocity rate (Vmax) of about 1 nmol/mg/min in RBE4 cells. The kinetic constants of the L-arginine uptake, representing system y+ transport activity, into RBE4 cells were determined with a Kt value of about 55 µM and a Vmax of 0.56 nmol/mg/min. Furthermore the expression of two sodium dependent transporters, the 5-HT transporter (SERT) and the organic cation/carnitine transporter OCTN2, was shown at the RBE4 cells. Uptake studies with radiolabeled 5-HT exhibited a saturable, sodium dependent transport at RBE4 cells with a Kt value of about 0.40 µM and a Vmax of about 52 fmol/mg/min. L-carnitine and TEA (tetraethylammonium) are known to be transported by the OCTN2 transporter. The uptake of L-carnitine into RBE4 cells was shown to be sodium dependent and saturable with a Kt value of 54 µM and a maximal velocity of about 3.6 pmol/mg/min. In contrast, the organic cation TEA follows a sodium independent uptake mechanism at RBE4 cells. Also a sodium independent choline uptake into the cells was discovered but the molecular identity remained unknown. This saturable choline transport exhibited a Kt value of about 22 µM and a maximal velocity of about 52 pmol/mg/min.
|
Page generated in 0.022 seconds