Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin

In the normal fed rat, both 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase and HMG-CoA reductase are found in high concentrations in hepatocytes that are localized periportally. The majority of the liver cells show little or no evidence of either enzyme. Addition of cholestyramine and mevinolin t...

Full description

Bibliographic Details
Main Authors: A C Li, R D Tanaka, K Callaway, A M Fogelman, P A Edwards
Format: Article
Language:English
Published: Elsevier 1988-06-01
Series:Journal of Lipid Research
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520384911
id doaj-4ab7064cdfcb4d32a1c30ffe1e50f2d2
record_format Article
spelling doaj-4ab7064cdfcb4d32a1c30ffe1e50f2d22021-04-25T04:19:29ZengElsevierJournal of Lipid Research0022-22751988-06-01296781796Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolinA C Li0R D Tanaka1K Callaway2A M Fogelman3P A Edwards4Department of Medicine, School of Public Health, University of California Los Angeles 90024.Department of Medicine, School of Public Health, University of California Los Angeles 90024.Department of Medicine, School of Public Health, University of California Los Angeles 90024.Department of Medicine, School of Public Health, University of California Los Angeles 90024.Department of Medicine, School of Public Health, University of California Los Angeles 90024.In the normal fed rat, both 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase and HMG-CoA reductase are found in high concentrations in hepatocytes that are localized periportally. The majority of the liver cells show little or no evidence of either enzyme. Addition of cholestyramine and mevinolin to the diet resulted in all liver cells showing strong positive staining for both HMG-CoA reductase and HMG-CoA synthase. These two drugs increased the hepatic HMG-CoA reductase and HMG-CoA synthase activities 92- and 6-fold, respectively, and also increased the HMG-CoA reductase activity in intestine, heart, and kidney 3- to 15-fold. We used immunofluorescence and avidin-biotin labeled antibody to localize HMG-CoA reductase in the rat intestine. In rats fed a normal diet, the most HMG-CoA reductase-positive cells were the villi of the ileum greater than jejunum greater than duodenum. Crypt cells showed no evidence of HMG-CoA reductase. Addition of cholestyramine and mevinolin to the diet led to a dramatic increase in the concentration of HMG-CoA reductase in the apical region of the villi of the ileum and jejunum and in the crypt cells of the duodenum. Hence these two drugs affected both the relative concentration and distribution of intestinal HMG-CoA reductase. Cholestyramine and mevinolin feeding induced in the liver, but not intestine, whorls of smooth endoplasmic reticulum that were proximal to the nucleus and contained high concentrations of HMG-CoA reductase. Administration of mevalonolactone led to the rapid dissolution of the hepatic whorls within 15 min, at a time when there is little or no change in the mass of HMG-CoA reductase. We conclude that the whorls are present in the livers of rats fed cholestyramine and mevinolin because the cells are deprived of a cellular product normally synthesized from mevalonate.http://www.sciencedirect.com/science/article/pii/S0022227520384911
collection DOAJ
language English
format Article
sources DOAJ
author A C Li
R D Tanaka
K Callaway
A M Fogelman
P A Edwards
spellingShingle A C Li
R D Tanaka
K Callaway
A M Fogelman
P A Edwards
Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
Journal of Lipid Research
author_facet A C Li
R D Tanaka
K Callaway
A M Fogelman
P A Edwards
author_sort A C Li
title Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
title_short Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
title_full Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
title_fullStr Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
title_full_unstemmed Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3-methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
title_sort localization of 3-hydroxy-3-methylglutaryl coa reductase and 3-hydroxy-3-methylglutaryl coa synthase in the rat liver and intestine is affected by cholestyramine and mevinolin
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 1988-06-01
description In the normal fed rat, both 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase and HMG-CoA reductase are found in high concentrations in hepatocytes that are localized periportally. The majority of the liver cells show little or no evidence of either enzyme. Addition of cholestyramine and mevinolin to the diet resulted in all liver cells showing strong positive staining for both HMG-CoA reductase and HMG-CoA synthase. These two drugs increased the hepatic HMG-CoA reductase and HMG-CoA synthase activities 92- and 6-fold, respectively, and also increased the HMG-CoA reductase activity in intestine, heart, and kidney 3- to 15-fold. We used immunofluorescence and avidin-biotin labeled antibody to localize HMG-CoA reductase in the rat intestine. In rats fed a normal diet, the most HMG-CoA reductase-positive cells were the villi of the ileum greater than jejunum greater than duodenum. Crypt cells showed no evidence of HMG-CoA reductase. Addition of cholestyramine and mevinolin to the diet led to a dramatic increase in the concentration of HMG-CoA reductase in the apical region of the villi of the ileum and jejunum and in the crypt cells of the duodenum. Hence these two drugs affected both the relative concentration and distribution of intestinal HMG-CoA reductase. Cholestyramine and mevinolin feeding induced in the liver, but not intestine, whorls of smooth endoplasmic reticulum that were proximal to the nucleus and contained high concentrations of HMG-CoA reductase. Administration of mevalonolactone led to the rapid dissolution of the hepatic whorls within 15 min, at a time when there is little or no change in the mass of HMG-CoA reductase. We conclude that the whorls are present in the livers of rats fed cholestyramine and mevinolin because the cells are deprived of a cellular product normally synthesized from mevalonate.
url http://www.sciencedirect.com/science/article/pii/S0022227520384911
work_keys_str_mv AT acli localizationof3hydroxy3methylglutarylcoareductaseand3hydroxy3methylglutarylcoasynthaseintheratliverandintestineisaffectedbycholestyramineandmevinolin
AT rdtanaka localizationof3hydroxy3methylglutarylcoareductaseand3hydroxy3methylglutarylcoasynthaseintheratliverandintestineisaffectedbycholestyramineandmevinolin
AT kcallaway localizationof3hydroxy3methylglutarylcoareductaseand3hydroxy3methylglutarylcoasynthaseintheratliverandintestineisaffectedbycholestyramineandmevinolin
AT amfogelman localizationof3hydroxy3methylglutarylcoareductaseand3hydroxy3methylglutarylcoasynthaseintheratliverandintestineisaffectedbycholestyramineandmevinolin
AT paedwards localizationof3hydroxy3methylglutarylcoareductaseand3hydroxy3methylglutarylcoasynthaseintheratliverandintestineisaffectedbycholestyramineandmevinolin
_version_ 1721510446818656256