Protein and m-RNA expression of farnesyl-transferases, RhoA and RhoB in rat liver hepatocytes: action of perillyl alcohol and vitamin A in vivo.
We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases alpha and beta subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase alpha protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase alpha protein. FTase beta protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals.
Bassi
A M
AM
Department of Experimental Medicine, Section of General Pathology, University of Genoa, Via L.B. Alberti 2, 16132, Genoa, Italy. ambassi@medicina.unige.it
Romano
P
P
Mangini
S
S
Colombo
M
M
Canepa
C
C
Nanni
G
G
Casu
A
A
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D000818:Animals; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D039821:Monoterpenes / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014801:Vitamin A / Q000378:metabolism / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*
D039821:Monoterpenes; D012333:RNA, Messenger; D014801:Vitamin A; C032208:perillyl alcohol; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein