L‐carnitine increases cell proliferation and amino acid transporter expression via the activation of insulin‐like growth factor I signaling pathway in rat trophoblast cells

Abstract

Early embryo implantation and development is primarily determined by the homeostasis between cellular apoptosis and proliferation as well as placental nutrient transporters. Recent studies showed that L‐carnitine enhances female reproductive performance. However, the potential function of L‐carnitine on placenta is largely unknown. In our study, primary rat trophoblast cells were separated and cultured for 12 hr in medium containing various concentrations of L‐carnitine (0, 1, 10, and 50 mM). Placenta trophoblast cells treated with 50 mM L‐carnitine increased the proportion of cells in S phase of the cell cycle ( p < .05). In addition, live cell percentage was increased when treated with either 10 mM or 50 mM L‐carnitine, which was accompanied with decreased necrotic cells, late apoptotic cells, and early apoptotic cells ( p < .05). Compared with the control treatment, the mRNA expression of insulin‐like growth factor I (IGF‐1) and insulin‐like growth factor I receptor (IGF‐1R) was higher in rat placenta trophoblasts treated with either 10 mM or 50 mM L‐carnitine ( p < .05). Similarly, sodium‐dependent neutral amino acid transporter (SNAT)‐1 and SNAT2 were up‐regulated in both mRNA and protein levels when trophoblast cells were treated with 50 mM L‐carnitine ( p < .05). Inhibiting downstream targets (Akt or ERK signaling pathways) of IGF‐1 signaling pathway partially blocked the effect the L‐carnitine‐induced increase in protein abundances of SNAT1 and SNAT2. Collectively, our data showed protective role of L‐carnitine on placenta trophoblast cells through the involvement of IGF‐1 signaling pathway.

The Protective Effects of Acetyl L-Carnitine for The Offspring and Lactating Moms of Rats Received Bromocriptine

“…In contrast, dopamine agonists like bromocriptine, which is used to treat disorders linked to hyperprolactinemia, reduce the amount of prolactin that is produced [35,36]. While treatment with carnitine alone or with carnitine and bromocriptine restored the normal structure of secretory acini, intralobular channels, channels between lobes, and blood vessels, the amino acid carnitine is essential for both cellular proliferation and apoptosis due to its stimulating effect on mitochondria and inhibition of TNF and other antiproliferative molecules [37]. According to [38] it appears that ALCAR reduced the amount of cytochrome C in the cytosol, which in turn activated caspase-3 [38,39] and protected cells from lipid peroxidation and mitochondrial membrane collapse under stressful circumstances [40,41].…”

Maternal Serum and Placental Metabolomes in Association with Prenatal Phthalate Exposure and Neurodevelopmental Outcomes in the MARBLES Cohort

“…Thus, lower carnitine and O-acetylcarnitine concentrations with increasing exposure to the phthalate mixture could reflect impaired placental lipid transport and might suggest, in conjunction with evidence of oxidative stress, impaired mitochondrial function. Moreover, carnitine increases cell proliferation and amino acid transporter expression and abundance through insulin-like growth factor I signaling in rat trophoblasts [65]. Carnitine is essential to fetal development [66].…”