3-Hydroxy-3-methylglutaryl coenzyme A reductase in rainbow trout: effects of fasting and statin drugs on activities and mRNA transcripts.
Human pharmaceuticals including statin drugs are found in effluents post-waste water treatment plant. In order to establish whether statin drugs could affect an aquatic species, we initially characterized in the rainbow trout the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase or HMGCoAR which is the mammalian target of statin drugs. Two HMGCoAR transcripts (-1 and -2) were isolated to trout tissues and given their prevalence in liver and brain, these two tissues were used in activity assays. HMGCoAR activities were 87.2 and 66.0 pmol/min/mg protein for liver microsomes and whole brain homogenates. Liver activities were affected by conditions promoting phosphorylation but not by a 14 day fast; brain activities were differentially altered by fasting and re-feeding. Even though activities were altered by fasting, HMGCoAR-1 (but not -2) mRNA was reduced by fasting in both the liver and hypothalamus/pituitary. Both statin drugs (cerivastatin and atorvastatin) significantly decreased HMGCoAR activities in vitro and cerivastatin when injected significantly decreased hepatic but not brain activities; some changes in mRNA levels were noted. These studies demonstrate that at the concentrations of statins used in this study, effects on HMGCoAR activities and transcripts occur. Such changes could affect cholesterol content and may alter cholesterol dynamics in this species.
Estey
Chelsie
C
Department of Biology, and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5.
Chen
Xi
X
Moon
Thomas W
TW
D000595:Amino Acid Sequence; D000818:Animals; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; D011725:Pyridines; D011758:Pyrroles; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D002784:Cholesterol; D000069059:Atorvastatin; C086276:cerivastatin; D006903:Hydroxymethylglutaryl CoA Reductases