Cadmium suppresses delta 9 desaturase activity in rat hepatocytes.
The effects of cadmium (Cd) on the fatty acid composition and delta 9 desaturation activity were studied in hepatocytes which had been cultured in serum-free medium. The aim of this study was to determine whether the inhibition of delta 9 desaturase seen in Cd-treated rat liver (Kudo et al. (1991) Toxicology, 68, 133-142) is the direct effect of Cd or not. When hepatocytes were cultured in serum-free medium, increases in the proportions of monounsaturated fatty acids such as oleic acid (18:1) were observed in the phospholipid (PL) and triacylglycerol (TG) fractions of hepatocytes, suggesting that delta 9 desaturase was induced. By contrast, essential fatty acids such as linoleic acid (18:2) and arachidonic acid (20:4) decreased. These changes were similar to those seen in the livers of essential fatty acid (EFA)-deficient rats. When hepatocytes were cultured in the presence of CdCl2, the changes in the fatty acid composition were suppressed. The effect of CdCl2 was concentration-dependent. The rate of the conversion of 18:0 to 18:1, which is catalyzed by delta 9 desaturase, was reduced by treatment with Cd, whereas the rate of conversion of 18:2 to 20:4, which is catalyzed by delta 6 desaturase, was slightly increased. Cd did not inhibit liver microsomal delta 9 desaturase activity in vitro. We concluded that Cd suppressed the induction of delta 9 desaturase in cultured hepatocytes. These phenomena can explain the selective inhibition of delta 9 desaturase in the livers of Cd-treated rats.
Kudo
N
N
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Waku
K
K
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002478:Cells, Cultured / Q000737:chemistry; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase
D016895:Culture Media, Serum-Free; D005227:Fatty Acids; D010743:Phospholipids; D002104:Cadmium; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase