Differential regulation by a peroxisome proliferator of the different multifunctional proteins in guinea pig: cDNA cloning of the guinea pig D-specific multifunctional protein 2.
After our previous report on the cloning of two cDNA species in guinea pig, both encoding the same hepatic 79 kDa multifunctional protein 1 (MFP-1) [Caira, Cherkaoui-Malki, Hoefler and Latruffe (1996) FEBS Lett. 378, 57-60], here we report the cloning of a cDNA encoding a second multifunctional peroxisomal protein (MFP-2) in guinea-pig liver. This 2356 nt cDNA encodes a protein of 735 residues (79.7 kDa) whose sequence shows 83% identity with rat MFP-2 [Dieuaide-Noubhani, Novikov, Baumgart, Vanhooren, Fransen, Goethals, Vandekerckhove, Van Veldhoven and Mannaerts (1996) Eur. J. Biochem. 240, 660-666]. In parallel, we studied the effect of ciprofibrate, a hypolipaemic agent also known as peroxisome proliferator in rodent, on the expression of MFP-1 and MFP-2 (2.6 kb) in rats and guinea pigs. By Northern blotting analysis we demonstrated that three MFP-1-related mRNA species are expressed in the guinea-pig liver. The expression of two of them (3.5 and 2.6 kb) is slightly increased by ciprofibrate, whereas the 3.0 kb MFP-1 mRNA is, unlike the rat one, strongly down-regulated in guinea pigs treated with ciprofibrate. In a similar way, the hepatic expression of the guinea-pig 2.6 kb MFP-2 mRNA is also down-regulated in guinea pigs treated with ciprofibrate. These results demonstrate (1) that in contrast with the unique 3.0 kb MFP-1 rat mRNA, at least three hepatic MFP-1-related mRNA species are co-expressed in guinea pig; and (2) that, opposed to the accepted idea of non-responsiveness of the guinea pig to ciprofibrate, this drug affects MFP-1 and MFP-2 gene expression in this species. Also, the mRNA species for acyl-CoA oxidase and thiolase, two other enzymes of the peroxisomal beta-oxidation pathway that are induced severalfold in responsive species are down-regulated in guinea pig. This paper is the first, to our knowledge, reporting the down-regulation of the expression of genes encoding enzymes involved in the peroxisomal beta-oxidation of fatty acids (MFP-1) and bile acid synthesis (MFP-2) in mammals.
Caira
F
F
Laboratoire de Biologie Moléculaire et Cellulaire, Faculté des Sciences, Université de Bourgogne, BP400, 21011 Dijon Cedex, France.
Clémencet
M C
MC
Cherkaoui-Malki
M
M
Dieuaide-Noubhani
M
M
Pacot
C
C
Van Veldhoven
P P
PP
Latruffe
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D004960:Estradiol Dehydrogenases / Q000096:biosynthesis* / Q000737:chemistry; D058607:Fibric Acids; D005786:Gene Expression Regulation / Q000187:drug effects*; D006168:Guinea Pigs; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects
D018076:DNA, Complementary; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D002995:Clofibric Acid; D010088:Oxidoreductases; D004960:Estradiol Dehydrogenases; D004746:Enoyl-CoA Hydratase; C019304:ciprofibrate