Lipid Transfer Protein Genes Are Differently Expressed in Rat Soleus Muscle at Early and Later Periods of Muscle Disuse

Abstract

This work reports analysis of lipid transfer protein (LTPs) mRNA levels in rat soleus muscle after 12-h and 14-day hindlimb suspension (HS). The LTP genes of interest were as follows: ceramide transporter 1 (CERT1), ceramide-1-phosphate transporter protein (CPTP), sphingosine-1-phosphate transporter (Protein spinster homolog 2—SPNS2), four-phosphate adaptor protein 2 (FAPP2) transferring glucosylceramide, and oxysterol-binding proteins OSBP and ORP4 (family I of OSBP-related proteins). LTP mRNA expression was analyzed using RT-PCR. Early changes in the expression of LTP genes after 12-h HS were characterized by the dramatic decrease in mRNA content of CERT1, CPTP, SPNS2 and ORP4 genes. In contrast, the expression of the FAPP2 gene was increased, whereas OSBP mRNA content did not change as compared to the control level. After the 14-day HS only CERT1 and CPTP mRNA levels remained decreased while expression of other LTP genes did not significantly differ from the control values. Clomipramine treatment did not affect sphingolipid transporters and OSBPs at the early period of HS, but notably enhanced the expression of CERT1, CPTP, FAPP2, and both OSBPs genes in soleus muscle of rats subjected to 14-day unloading. Our data indicate that short-term and long-term muscle unloading differently affects the expression of genes encoding LTPs for sphingolipid and cholesterol intracellular transport. Only ceramide and ceramide-1-phosphate transporters were decreased at both periods of disuse. Taking into account our previous data about acid sphingomyelinase (aSMase) and ceramide up-regulation in the unloaded soleus muscle, as well as a normalizing effect of clomipramine on both high ceramide level and low expression of its transporters at 14-day HS, we can assume that there must be a feedback mechanism in regulation of CERT1 and CPTP genes expression in case of ceramide accumulation caused by disuse.