INVESTIGADORES
FAVALE Nicolas Octavio
congresos y reuniones científicas
Título:
Regulation of the sphingolipid metabolism during MDCK cell differentiation
Autor/es:
LUCILA G. PESCIO; NICOLÁS O. FAVALE ; NORMA B. STERIN-SPEZIALE
Lugar:
Bilbao
Reunión:
Conferencia; International Conference on the Bioscience of Lipids; 2010
Institución organizadora:
ICBL
Resumen:
We have previously
reported that hypertonicity induces MDCK cell differentiation by a glycosphingolipid
(GSL) dependent mechanism.
While GSLs predominate in the apical membrane, sphingomyelin (SM) is the major
sphingolipid (SL) of the basolateral membrane. Ceramide (Cer) is the substrate for GSLs and SM,
and it can stem from the de novo synthesis
(Cycloserine (CS) sensitive) or the salvage pathway. Both pathways are
Fumonisin B1 (FB1) sensitive. In this study we evaluate how the source of Cer
is channelled to GSLs or SM under differentiation-induced condition. Confluent
MDCK cells cultured under high NaCl concentration media (hypertonicity) or kept
in isotonicity (control) were incubated in the presence or absence of CS, FB1
or PDMP (a GSL synthesis inhibitor), and SL metabolism was determined by using
[14C]Palmitic Acid and [14C]Galactose as radioactive
precursors. [14C]SM and [14C]GSLs showed basal levels,
sensitive to CS and FB1, under control conditions. GSL synthesis was also
inhibited by PDMP. At early stage of differentiation there was an increase in
GSL synthesis CS- and FB1-resistant. However, [14C]SM showed an
increase in an advanced stage of differentiation, which was CS- and
FB1-sensitive and regulable by PDMP. The results demonstrate that under control
conditions GSLs and SM shared the same pool of Cer, whereas under an early
stage of differentiation Cer was channelled to GSL synthesis by the salvage
pathway and, in later times of differentiation Cer was used to synthesize SM. From these results we conclude that hypertonicity displays a specific SL
program required for the differentiation of MDCK cells.