Fatty acid delta(5)-desaturase mRNA is regulated by dietary vitamin A and exogenous retinoic acid in liver of adult rats.
Delta(5)-Desaturase (D5D) catalyzes the Delta(5,6) desaturation of dietary essential fatty acids of the n-6 and n-3 series. By subtraction hybridization of vitamin A (VA)-deficient and control rat liver cDNA libraries, we isolated a 106-bp cDNA fragment that proved to be homologous to human liver D5D cDNA and used it as a probe to analyze rat D5D mRNA and clone the rat full-length cDNA. Delta(5)-Desaturase mRNA was threefold more abundant in liver from VA-deficient rats than in liver from VA-sufficient rats and was expressed dose dependently when dietary VA was varied (VA marginal > control > VA supplemented). Treatment of VA-deficient rats with all-trans-retinoic acid lowered the level of expression of D5D mRNA toward that of VA-sufficient rats. The 3413-bp full-length D5D cDNA cloned from rat liver contains an open reading frame of 447 amino acid residues sharing 92% similarity with its human counterpart. Expression of this cDNA in HEK293T cells incubated with dihomo-gamma-linolenic acid (20:3, n-6) resulted in a significantly increased ratio of the product, arachidonic acid (20:4, n-6), to substrate in cell lipid extracts. Delta(5)-Desaturase mRNA is expressed in relatively high abundance in rat adrenal gland and mammary tissue and moderately in liver, kidney, lung, spleen, thymus, brain, and eye. The regulation of D5D by VA could be important for growth and development, and reproduction, as well as in the control of inflammation.
Zolfaghari
R
R
Department of Nutrition, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Cifelli
C J
CJ
Banta
M D
MD
Ross
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000090943:Delta-5 Fatty Acid Desaturase; D019587:Dietary Supplements; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*
D000090943:Delta-5 Fatty Acid Desaturase; D012333:RNA, Messenger; D014801:Vitamin A; D014212:Tretinoin; D044943:Fatty Acid Desaturases