| Summary: | 碩士 === 國立臺灣大學 === 藥學研究所 === 94 === L-carnitine is important for beta-oxidation of fatty acids and intracellular coenzyme A homeostasis. Given that the carnitine biosynthesis is immature in fetal organisms, it is pivotal for fetal organism to acquire carnitine to maintain normal functions. It is known that carnitine is mainly transported across placenta via organic cation transporter novel type II (OCTN2), a high affinity and sodium dependent carnitine transporter. BeWo cell is derived from human choriocarcinoma and can be induced to differentiate into syncytiotrophoblast by forskolin and has therefore been used as an in vitro placenta model. In the current study, BeWo treated with forskolin was used as a model for syncytiotrophoblast. Results from RT-PCR analysis showed that the expression level of OCTN2 was downregulated after 100 uM forskolin treatment. Uptake of 3H-labeled L-carnitine was sodium dependent and saturable (Km = 27.1 ± 11.8 uM, Vmax = 702 ± 132 pmol/30 min/mg protein) with a non-saturable constant k equals to 6.02 ± 1.21 (uL/30 min/mg protein). The values of kinetic parameters changed after forskolin treatment (Km = 72.6 ± 5.4 uM, Vmax = 1805 ± 420 pmol/30 min/mg protein, k = 2.25 ± 0.59 uL/30 min/mg protein). These results suggest that the expression level and function of OCTN2 are both changed during syncytialisation. IC50 for several drugs of carnitine uptake were also determinated to understand the effect on drug-OCTN2 interaction during syncytialisation induced by forskolin.
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