Abstract
Sphingosine-1-phosphate (S1P) has been reported as a matriptase activator. The aim of this study was to reveal if S1P can influence hepcidin production. Furthermore, we investigated how S1P can affect the viability and the redox status of primary hepatocytes. Rat primary hepatocytes were cultivated for 72 h and were treated with 50, 200, 1000 ng/ml S1P. Cell-free supernatants were collected every 24 h. Cell viability was tested by a colorimetric method using tetrazolium compound (MTS). The hepcidin levels in the cell-free supernatants were examined with hepcidin sandwich ELISA to determine the effect of S1P on the hepcidin-modulating ability of matriptase. In order to estimate the extent of S1P-generated oxidative stress, extracellular H2O2 measurements were performed by the use of fluorescent dye. Based on the findings, S1P treatment did not cause cell death for 72 h at concentrations up to 1000 ng/ml. S1P did not influence the extracellular H2O2 production for 72 h. The hepcidin levels were significantly suppressed in hepatocytes exposed to S1P treatment. Further studies would be needed to explore the exact mechanism of action of S1P.
Highlights
Sphingosine-1-phosphate (S1P) has been reported as a matriptase activator
It was found that S1P administration for 72 h even at 1000 ng/ml was safe in the case of the rat primary hepatocyte model
We found that S1P did not cause a significant increase in the extracellular H2O2 levels at any applied concentrations within the investigated time period (P > 0.05 in each case) (Fig. 2)
Summary
The aim of this study was to reveal if S1P can influence hepcidin production. Rat primary hepatocytes were cultivated for 72 h and were treated with 50, 200, 1000 ng/ml S1P. The hepcidin levels in the cell-free supernatants were examined with hepcidin sandwich ELISA to determine the effect of S1P on the hepcidin-modulating ability of matriptase. The hepcidin levels were significantly suppressed in hepatocytes exposed to S1P treatment. Transformed hepatocyte cell lines, for example rat hepatoma H-4-II-E cells (Kovacs et al, 1977) cannot adequately mimic the phenotype of the liver. The rat primary hepatocyte model is an important tool for hepatic toxicology studies. It is well reported that primary cells have a limited lifetime (2–4 days) (Soldatow et al, 2013). According to Oberst et al (2001), MT-1 has a potential role in cancer invasion and metastasis in some types of cancer
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