Expression of glucose transporters in the developing rat skin.

We found the changed distribution of glucose transporter (GLUT) proteins in the skin during rat development. At 15 days of gestation, GLUT1 and 2 proteins were expressed in the stratum corneum of epidermal cells. In postnatal skin, however, GLUT1 and 2 exhibit different expression patterns. While GLUT1 expression becomes more restricted to the stratum basale with development, GLUT2 was found mainly in stratum spinosum and granulosum, but not being localized in the stratum basale at any stages of perinatal skin development. Considering all these, it can be speculated that each GLUT protein plays its specific role in different epidermal layers and that the glucose used in mammalian skin in utero could be originated from the amniotic fluid during skin development.

Immunohistochemical study on the distribution of sodium-dependent vitamin C transporters in the respiratory system of adult rat.

As vitamin C (L-ascorbic acid, VC) is known to be essential for many enzymatic reactions, the study on the transport mechanism of VC through cytoplasmic membrane is crucial to understanding physiological role of VC in cells and the respiratory system. In this regard, the study on the newly identified sodium-dependent VC transporters (SVCTs), SVCT1 and SVCT2, is required in organs that contain high concentration of VC. We have shown the distribution of SVCT proteins in the respiratory system, which has been reported to be one of the organs with a high concentration of VC, using immunohistochemical techniques. In the present study, intense SVCT immunoreactivities (IRs) were mainly localized in the respiratory system epithelial cells. In the trachea, both SVCT1 and 2 were localized in the psuedostratified ciliated columnar epithelium. In the terminal bronchiole, SVCT1 and 2 IRs were mainly observed in the apical portion of the simple columnar epithelium. In addition, SVCT IRs was localized within the cell membrane of some alveolar cells, even though we could not identify the exact cell types. These results provide the first evidence that intense SVCT1 and 2 IRs were found in the apical portion of the respiratory epithelial cells, suggesting that SVCT proteins in the apical portion could transport the reduced form of VC included in the airway surface liquid into the respiratory epithelial cells.

Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake.

Sodium ascorbate (vitamin C) has a reputation for inconsistent effects upon malignant tumor cells, which vary from growth stimulation to apoptosis induction. Melanoma cells were found to be more susceptible to vitamin C toxicity than any other tumor cells. The present study has shown that sodium ascorbate decreases cellular iron uptake by melanoma cells in a dose- and time-dependent fashion, indicating that intracellular iron levels may be a critical factor in sodium ascorbate-induced apoptosis. Indeed, sodium ascorbate-induced apoptosis is enhanced by the iron chelator, desferrioxamine (DFO) while it is inhibited by the iron donor, ferric ammonium citrate (FAC). Moreover, the inhibitory effects of sodium ascorbate on intracellular iron levels are blocked by addition of transferrin, suggesting that transferrin receptor (TfR) dependent pathway of iron uptake may be regulated by sodium ascorbate. Cells exposed to sodium ascorbate demonstrated down-regulation of TfR expression and this precedes sodium ascorbate-induced apoptosis. Taken together, sodium ascorbate-mediated apoptosis appears to be initiated by a reduction of TfR expression, resulting in a down-regulation of iron uptake followed by an induction of apoptosis. This study demonstrates the specific mechanism of sodium ascorbate-induced apoptosis and these findings support future clinical trial of sodium ascorbate in the prevention of human melanoma relapse.