Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Colestipol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1999

Pruritus.

The treatment of patients with pruritus of liver disease poses a challenge to the clinician. Resins (cholestyramine or colestipol) in quantities of 4 to 16 grams a day should be the initial agents used. In those who remain refractory, diphenhydramine should be added, although sedation may limit the use of higher doses. If symptoms still persist, rifampin up to 600 mg/day can be added to the above regimen with close monitoring of hepatic function. If, despite this combination, pruritus persists and quality of life remains poor, experimental therapies in the form of oral opioid antagonists, and orthotopic liver transplantation should be considered.

Journal Article↗
PubMed1990

Pharmacotherapy of disorders of plasma lipoprotein metabolism.

Pharmacologic intervention for altering plasma lipoproteins is aimed principally at reducing atherogenesis and thereby preventing coronary artery disease. These drugs should be prescribed only after nonpharmacologic interventions (reduction of saturated fat and cholesterol consumption, weight reduction, aerobic exercise, cessation of cigarette smoking) have failed to achieve an adequate effect. The plasma concentration of the atherogenic low-density lipoprotein (LDL) may be reduced in hypercholesterolemic patients by increasing hepatic LDL receptor synthesis (bile acid sequestering resins, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) or by reducing hepatic very low density lipoprotein synthesis (gemfibrozil, nicotinic acid). LDL concentration may also be reduced by treatment with one of the fibrates (e.g., fenofibrate). Several classes of lipid-lowering drugs also increase the plasma high-density lipoprotein (HDL) cholesterol concentration. In the case of the fibrates, this appears to be principally mediated through an increase in lipoprotein lipase activity. Gemfibrozil additionally stimulates apolipoprotein AI synthesis. The increase in HDL cholesterol produced by nicotinic acid is due primarily to decreased clearance of HDL particles from the circulation. The increase in HDL concentration produced by gemfibrozil was shown in the Helsinki Heart Study to make a major contribution to a reduced incidence of coronary artery disease, independently of that made by the decrease in LDL. The Cholesterol-Lowering Atherosclerosis Study demonstrated that combined therapy with a resin (colestipol) and nicotinic acid can reduce the progression of coronary atherosclerosis and the development of graft lesions in patients who have undergone coronary artery bypass graft surgery.

Apolipoproteins B↗
PubMed1993

How effective is drug therapy in heterozygous familial hypercholesterolemia?

The goals of drug therapy in adult patients with heterozygous familial hypercholesterolemia (FH) are directed at reducing plasma concentrations of low density lipoproteins (LDL), with a secondary goal in selected patients to concurrently decrease elevated plasma concentrations of lipoprotein(a), triglycerides, and potentially exert favorable effects on the concentrations of high density lipoproteins (HDL). Desirable goals of therapy are to reduce concentrations of LDL cholesterol to < 130-160 mg/dL in patients without evidence of coronary artery disease, and, in my opinion, to < 100 mg/dL in patients with evidence of coronary artery disease. The bile acid sequestrants, cholestyramine and colestipol, reduce LDL concentrations by 23-36%, when given in doses of 4-6 scoops/day, but reduce LDL concentrations to desirable levels in only 10-15% of patients. Similarly, nicotinic acid, in doses of 3-6 g/day, is capable of reducing LDL concentrations by up to 30%, but the majority of patients still remain hypercholesterolemic. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which include lovastatin, simvastatin, and pravastatin, are the most effective of the currently available drugs and show dose-dependent effects on the concentrations of LDL cholesterol, which decrease by 20-45% in response to these drugs when used over the full dosage range. However, even with these agents, concentrations of LDL cholesterol remain > 200 mg/dL in one-third of male and female patients with heterozygous FH and remain > 160 mg/dL in 75-80% of treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1993

Regulation of isoprenoid metabolism in rat liver: near constant chain lengths of dolichyl phosphate and ubiquinone are maintained during greatly altered rates of cholesterogenesis.

When rat liver slices were incubated with varying concentrations of [3H]mevalonolactone, the chain lengths of radiolabeled dolichyl phosphate and ubiquinone varied according to the initial mevalonolactone concentration, indicating that product chain length is dependent on the level of isoprenoid diphosphate intermediates. However, when livers were analyzed from rats which had been maintained on diets of either colestipol (which induces cholesterogenesis 3-fold), or normal chow, or cholesterol (which suppresses cholesterogenesis to 5% of normal) there were only minor changes in the isoprene distribution of either dolichyl phosphate or ubiquinone. In contrast, when rats were maintained on 2% cholesterol plus mevalonolactone (conditions prone to increase the levels of intermediates), the isoprene distributions of both of these compounds were greatly shifted to the higher homologs. However, under none of these conditions were the hepatic levels of these compounds changed significantly. It is concluded that under conditions of greatly altered cholesterogenesis, regulatory mechanisms exist which stabilize the levels of isoprenoid diphosphate intermediates, and that even when levels are increased (e.g., by dietary manipulation), the effect is only to alter isoprene distribution and not the rate of synthesis of dolichyl phosphate and ubiquinone.

Animals↗
PubMed1982

Effects of interruption of the enterohepatic circulation of bile acids on the transport of very low density-lipoprotein triglycerides.

An increase in plasma very low density lipoprotein-triglycerides (VLDL-TG) is seen frequently during treatment with bile acid-binding resins. The purpose of this study was to determine whether this increment in VLDL-TG is due mainly to an increase in synthesis of VLDL, or to an enhanced catabolism. Three types of patients were studied: (1) 7 normotriglyceridemic subjects. (2) 4 obese patients, and (3) 9 hypertriglyceridemic patients. Before treatment they underwent a study of VLDL-TG kinetics that employed multicompartmental analysis of specific activity curves following injection of 3H-glycerol. The patients were then treated with a bile acid-binding resin, either cholestyramine or colestipol, for several weeks to several months. At the end of the treatment period, they were readmitted to the hospital for a second study of VLDL-TG kinetics. The patients showed a variable response to resin therapy. Many had an increase in concentrations of VLDL-TG, but others had no change or even a slight decrease. However, analysis of the data showed a high correlation between change in production rates of VLDL-TG and change in concentration. Also, when the data for the 20 patients were combined, there was a statistically significant increase in both synthetic rates and concentrations of VLDL-TG; in contrast, the fractional catabolic rate (FCR) was unchanged by therapy. Therefore, our data show that when treatment with bile acid sequestrants causes an increase in plasma VLDL-TG, the increase is due to an increment in production and not to a decrease in catabolism.

Adult↗
PubMed1983

The effect of variable fat diets and cholesterol-lowering drugs on Antithrombin III levels in hyperlipoproteinemic and normal subjects.

Functional and immunological Antithrombin III (AT III) levels were studied in normal and hyperlipoproteinemic subjects undergoing crossover therapeutic trials of either diets or hypocholesterolemic drugs. The diet trial subjects, 7 hyperlipoproteinemics and 15 normals, were randomly assigned to crossover between a high saturated fat diet (P/S ratio 1:8) and a high polyunsaturated fat diet (P/S ratio 4:1) for periods of 6-8 weeks, preceded by a baseline period on regular American diet (P/S ratio 1:1). For the drug trials, 33 type II A or B hyperlipoproteinemics were treated in random and double-blind fashion with Colestipol (20 gm/day) or both, for periods of 3 months, preceded by a double placebo period. Mean low density lipoprotein cholesterol levels were significantly different (p less than 0.001) between high saturated and high polyunsaturated fat diets (157 +/- 37 mg/dl vs 137 +/- 31 mg/dl respectively, mean +/- S.D.) and between placebo and drug treatment periods (226 +/- 51 mg/dl vs 183 +/- 44 mg/dl respectively, mean + S.D.). There was no difference in basal functional or immunological AT III levels between normal and hyperlipoproteinemics. AT III levels did not correlate significantly with cholesterol or triglyceride levels and remained unchanged despite significant reductions in serum cholesterol related to the diet and drug therapy. There appears to be no significant association between baseline or post treatment serum cholesterol levels and functional or immunological AT III. Thus, changes in AT III are unlikely to play a role in the link between hypercholesterolemia and thrombosis.

Adult↗
PubMed1992

Effect of hypolipidemic drugs on cholinesterase activity in the rat.

1. The effect of four hypolipidemic agents with different mechanisms of action (fenofibrate, probucol, colestipol and nicotinic acid) on plasma and liver cholinesterase has been studied. 2. Liver weight and liver weight/body weight ratio increased only after treatment with fenofibrate. 3. Plasma and liver cholinesterase activity increased markedly after fenofibrate, a strong peroxisome proliferator, and slightly after nicotinic acid, a weak peroxisome proliferator. 4. The data obtained suggest that increased cholinesterase activity is due to increased rate of fatty acid oxidation caused by peroxisome proliferators.

Animals↗
PubMed1999

Niacin treatment increases plasma homocyst(e)ine levels.

BACKGROUND: Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. METHODS: The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. RESULTS: During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P <.0001). At 18 weeks after randomization, there was an absolute 55% increase from baseline in mean plasma homocyst(e)ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. CONCLUSIONS: Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

Aged↗
PubMed1995

Efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia.

PURPOSE: Patients with type I and type II diabetes mellitus have an increased risk of coronary heart disease. In many diabetics, hypercholesterolemia is present and further exacerbates this risk. We investigated the efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS: In this 24-week, multi-center, double-blind, placebo-controlled study, 94 patients (45 men, 49 women), 18 to 70 years of age, with type I or type II diabetes mellitus and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol [LDL-C] levels > 150 mg/dL and above the 75th percentile for the US population by age and gender) were randomized to receive pravastatin 20 mg hs or matching placebo. Two patients were randomized to treatment with drug for every 1 randomized to placebo. The dose could be doubled after 10 weeks, and cholestyramine or colestipol could be added after 18 weeks, as needed, to attempt to lower the LDL-C levels to below the 50th percentile for the US population. RESULTS: Significant reductions in LDL-C (-27.6%), total cholesterol (-22.1%), very-low-density lipoprotein cholesterol (-22.6%), and triglycerides (-12.8%) (P < or = 0.001 versus placebo for all reductions), and significant increases in high-density lipoprotein cholesterol (4.4%) (P < or = 0.05 versus placebo) were noted in the pravastatin treatment group (average dose 29.5 mg) at 16 weeks. The beneficial lipid-lowering effects of pravastatin were maintained throughout the 24 weeks of the study. Pravastatin was well tolerated, and the frequency of side effects was similar in the pravastatin and placebo groups. No clinically significant changes in the control of diabetes, as assessed by fasting blood glucose levels and glycosylated hemoglobin measurements, were seen during this study. CONCLUSION: The results of this study demonstrate that pravastatin is well tolerated and effective in lowering total cholesterol and LDL-C in patients with type I or type II diabetes mellitus and hypercholesterolemia.

Adult↗
PubMed1988

Management of lipids in primary and secondary prevention of cardiovascular diseases.

Although the frequency of cardiovascular disease is declining, it remains a major present and future threat to health in the United States. The deleterious effects of abnormal blood lipid concentrations have long been recognized, but the benefit of corrective intervention in this process has only recently been demonstrated. We review the major lipid abnormalities and the available clinical therapeutic interventions. In addition, we discuss data that address the premise that reducing low-density lipoprotein cholesterol or raising high-density lipoprotein cholesterol should decrease the progression of coronary atherosclerosis, and we summarize drug trials in which clofibrate, niacin, cholestyramine, and gemfibrozil decreased coronary heart disease events. Studies that used cholestyramine and the combination of colestipol and niacin resulted in decreased progression of coronary artery disease. On the basis of early experience with lovastatin, inhibitors of hydroxymethylglutaryl-coenzyme A reductase are likely to be effective in the treatment of hypercholesterolemia. The available information on the association of low cholesterol levels and cancer suggests that low total cholesterol is a consequence rather than a cause of carcinoma. Current data strongly support the concept of vigorous intervention directed at management of lipids, both with non-pharmacologic treatment and with drug therapy, for the primary and secondary prevention of coronary atherosclerosis.

Anticholesteremic Agents↗
PubMed1995

Currently available hypolipidaemic drugs and future therapeutic developments.

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.

Anticholesteremic Agents↗
PubMed1995

The pruritus of cholestasis.

The pruritus of cholestasis is a difficult clinical problem to manage. The pathogenesis of this symptom is unknown. All conventional therapies have been unsuccessful in isolating a particular group of substances that could be implicated as direct or indirect causative agents. It should be emphasized that nonspecific treatment modalities that lower the plasma concentrations of a variety of substances (such as cholestyramine, colestipol, charcoal hemoperfusion, plasmapheresis, partial external diversion of bile, and drugs that induce hepatic enzymes), can potentially ameliorate the pruritus of cholestasis by lowering the circulating levels of an undefined pruritogen or a factor responsible for inducing the primary mechanism of the pruritus. The encouraging results reported by the use of antibiotic therapy for this condition merits investigation. Increased opioidergic neurotransmission is part of the syndrome of cholestasis and it contributes, at least in part, to the pruritus associated with it. Opiate antagonists seem to be an effective alternative therapy for some patients. Recent preliminary reports suggest that other neurotransmitter systems, eg, serotoninergic, may be involved in the pruritus of cholestasis. The need for quantitation of scratching activity cannot be over emphasized. The use of quantitative methodology offers the opportunity to facilitate the study of scratching behavior that is a biological phenomenon secondary to liver disease.

Anti-Bacterial Agents↗
PubMed1987

Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels by L-triiodothyronine.

In hypophysectomized rats, hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, immunoreactive 97-kilodalton (97-kDa) protein, and mRNA were all reduced to undetectable levels. Administration of triiodothyronine (T3) resulted in large increases in all three after a 36-h lag period. HMG-CoA reductase activity, immunoreactive 97-kDa protein levels, and reductase mRNA levels were tightly correlated. Feeding hypophysectomized rats diets containing the bile acid sequestrant colestipol, together with the potent reductase inhibitor mevinolin, resulted in an increase in HMG-CoA reductase activity similar to that seen with T3 but a lesser stimulation of reductase mRNA levels. These results suggest that agents which cause depletion of mevalonate-derived products may share in part with T3 a common mechanism for increasing levels of HMG-CoA reductase activity in order to satisfy cellular needs for these products. Dexamethasone treatment, which is known to prevent the T3-mediated stimulation of reductase activity, caused a marked decrease in 97-kDa immunoreactive material but had little effect on reductase mRNA levels.

Animals↗
PubMed1989

Treatment of nephrotic hyperlipoproteinemia with gemfibrozil.

Hypercholesterolemia is a known complication of the nephrotic syndrome. Patients with persistent proteinuria and prolonged hypercholesterolemia are probably at increased risk for cardiovascular disease. Until recently there has been no safe and effective treatment for this disorder. The effects of gemfibrozil on plasma lipids and lipoproteins in hypercholesterolemic patients with the nephrotic syndrome were therefore studied. Eleven patients with the nephrotic syndrome were studied in a randomized, double-blind placebo-controlled trial with six-week treatment periods. Gemfibrozil 600 mg or placebo was administered twice a day. There was a third unblinded period in which seven patients received gemfibrozil plus the bile acid-binding resin, colestipol, 10 grams twice a day. Gemfibrozil treatment produced a marked reduction in plasma triglyceride (51%, P = 0.001) and a 15% decrease in plasma total cholesterol (P = 0.003). Low density lipoprotein cholesterol decreased 13% (P greater than 0.05), high density lipoprotein cholesterol increased 18% (P = 0.006) and the ratio of low density lipoprotein to high density lipoprotein cholesterol fell 26% (P = 0.01). Apolipoprotein A-l was unchanged while apolipoprotein B decreased 26% (P = 0.006). Four patients were unable to complete period 3 because of gastrointestinal symptoms. The remaining patients had further improvement in plasma lipids and lipoproteins with the combined therapy: total cholesterol further decreased 26%, triglycerides decreased 17%, low-density lipoprotein cholesterol decreased 36%, high-density lipoprotein to high-density lipoprotein cholesterol fell 33%. Gemfibrozil improved lipid and lipoprotein cardiovascular risk factors without major toxicity. Persistent elevations in total plasma and low-density lipoprotein cholesterol during gemfibrozil treatment, however, indicate the need for individualized drug therapy.

Adult↗
PubMed2003

Systematic review: ursodeoxycholic acid--adverse effects and drug interactions.

BACKGROUND: Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking. AIM: As experimental data suggest a role of bile acids in the regulation of hepatic drug metabolism at both the transcriptional and post-transcriptional level, the literature was screened for adverse drug reactions and drug interactions related to ursodeoxycholic acid. METHODS: A systematic review of the literature was performed using a refined search strategy to evaluate the adverse effects of ursodeoxycholic acid and its interactions with other drugs. RESULTS: Ursodeoxycholic acid caused diarrhoea in a small proportion of patients. Rare skin reactions were due to drug adjuvants rather than the active substance. Decompensation of liver cirrhosis was reported after the administration of ursodeoxycholic acid in single cases of end-stage primary biliary cirrhosis. Recurrent right upper quadrant abdominal pain was incidentally observed. The absorption of ursodeoxycholic acid was impaired by colestyramine, colestimide, colestipol, aluminium hydroxide and smectite. Metabolic drug interactions were reported for the cytochrome P4503A substrates, ciclosporin, nitrendipine and dapsone. CONCLUSIONS: Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected.

Cholagogues and Choleretics↗
PubMed1998

A US military perspective.

This paper discusses lipid therapy decision-making at the population level within the United States (US) Military Health Services System. The US Military Health Services System serves approximately 8.2 million beneficiaries fairly representative of the general population. Of its $680 million annual pharmacy expenditure, $45-$50 million is spent on lipid-lowering drugs. The military Medical Treatment Facilities (MTF) carry a Tri-Service Drug Formulary list, which serves as a bare minimum to which individual facilities may add other agents. The Department of Defense Pharmacoeconomic Center (PEC) performs cost-effectiveness analyses, establishes the Tri-Service Drug Formulary list and the National Mail Order Pharmacy formulary list, and provides drug treatment guidelines. Hyperlipidemia treatment guidelines published by the Pharmacoeconomic Center in 1995, which recommend the use of niacin, colestipol, and pravastatin, are currently under revision to take into consideration new drugs and new information in the field of lipid-lowering therapies. Future changes to the MTF outpatient formulary management may include the introduction of a Basic Core List of essential agents and a Master Pharmaceutical Agent List comprising the only drugs from which facilities may choose to add to their Basic Core List. These changes are designed to standardize drug availability across military facilities to leverage market share for lower drug prices.

Journal Article↗
PubMed1997

Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver.

Cholesterol feeding reduces the mRNAs encoding multiple enzymes in the cholesterol biosynthetic pathway and the low density lipoprotein receptor in livers of hamsters. Here we show that cholesterol feeding also reduces the levels of the nuclear NH2-terminal domains of sterol regulatory element binding proteins (SREBPs), which activate transcription of sterol-regulated genes. We show that livers of hamsters, like those of mice and humans, predominantly produce SREBP-2 and the 1c isoform of SREBP-1. Both are produced as membrane-bound precursors that must be proteolyzed to release the transcriptionally active NH2-terminal domains. Diets containing 0.1% to 1.0% cholesterol decreased the amount of nuclear SREBP-1c without affecting the amount of the membrane precursor or its mRNA, suggesting that cholesterol inhibits the proteolytic processing of SREBP-1 in liver as it does in cultured cells. Cholesterol also appeared to reduce the proteolytic processing of SREBP-2. In addition, at high levels of dietary cholesterol the mRNA encoding SREBP-2 declined and the amount of the precursor also fell, suggesting that cholesterol accumulation also may inhibit transcription of the SREBP-2 gene. The high-cholesterol diets reduced the amount of low density lipoprotein receptor mRNA by 30% and produced a more profound 70-90% reduction in mRNAs encoding 3-hydroxy-3-methylglutaryl CoA synthase and reductase. Treatment with lovastatin and Colestipol, which increases hepatic demands for cholesterol, increased the amount of SREBP-2 mRNA as well as the precursor and nuclear forms of the protein. This treatment caused a reciprocal decline in SREBP-1c mRNA and protein. Considered together, these data suggest that SREBPs play important roles in controlling transcription of sterol-regulated genes in liver, as they do in cultured cells.

Amino Acid Sequence↗
PubMed1997

Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA.

The synthesis of essential 7alpha-hydroxylated bile acids in the liver is mediated by two pathways that involve distinct 7alpha-hydroxylases. One pathway is initiated in the endoplasmic reticulum by cholesterol 7alpha-hydroxylase, a well studied cytochrome P450 enzyme. A second pathway is initiated by a less well defined oxysterol 7alpha-hydroxylase. Here, we show that a mouse hepatic oxysterol 7alpha-hydroxylase is encoded by Cyp7b1, a cytochrome P450 cDNA originally isolated from the hippocampus. Expression of a Cyp7b1 cDNA in cultured cells produces an enzyme with the same biochemical and pharmacological properties as those of the hepatic oxysterol 7alpha-hydroxylase. Cyp7b1 mRNA and protein are induced in the third week of life commensurate with an increase in hepatic oxysterol 7alpha-hydroxylase activity. In the adult mouse, dietary cholesterol or colestipol induce cholesterol 7alpha-hydroxylase mRNA levels but do not affect oxysterol 7alpha-hydroxylase enzyme activity, mRNA, or protein levels. Cholesterol 7alpha-hydroxylase mRNA is reduced to undetectable levels in response to bile acids, whereas expression of oxysterol 7alpha-hydroxylase is modestly decreased. The liver thus maintains the capacity to synthesize 7alpha-hydroxylated bile acids regardless of dietary composition, underscoring the central role of 7alpha-hydroxylated bile acids in lipid metabolism.

Animals↗