Factors affecting the regulation of apo b secretion by liver cells

Hahn, Susan; Goldberg, David M.

doi:10.1002/jcla.1860090616

Cited by 7 publications

(4 citation statements)

References 147 publications

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“…It is well-established that apo B is required for the assembly and secretion of these TG-rich lipoproteins by liver cells, and that each particle contains a single apo B molecule (32). Although controversies still exist, most of the available data, as summarized in recent reviews (33)(34)(35)(36), indicate that regulation of apo B secretion is primarily a posttranslational event governed by the efficiency of translocation of the protein across the endoplasmic reticulum membrane and its association with lipids. Excess of apo B that does not associate appropriately with lipids inside the endoplasmic reticulum lumen is degraded rapidly.…”

Section: Discussionmentioning

confidence: 99%

Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes.

Kuipers¹,

Jong²,

Lin³

et al. 1997

J. Clin. Invest.

157

136

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To explore mechanisms underlying triglyceride (TG) accumulation in livers of chow-fed apo E-deficient mice (Kuipers, F., J.M. van Ree, M.H. Hofker, H. Wolters, G. In't Veld, R.J. Vonk, H.M.G. Princen, and L.M. Havekes. 1996. Hepatology. 24:241-247), we investigated the effects of apo E deficiency on secretion of VLDL-associated TG (a) in vivo in mice, (b) in isolated perfused mouse livers, and (c) in cultured mouse hepatocytes. (a) Hepatic VLDL-TG production rate in vivo, determined after Triton WR1339 injection, was reduced by 46% in apo E-deficient mice compared with controls. To eliminate the possibility that impaired VLDL secretion is caused by aspecific changes in hepatic function due to hypercholesterolemia, VLDL-TG production rates were also measured in apo E-deficient mice after transplantation of wild-type mouse bone marrow. Bone marrow- transplanted apo E-deficient mice, which do not express apo E in hepatocytes, showed normalized plasma cholesterol levels, but VLDL-TG production was reduced by 59%. (b) VLDL-TG production by isolated perfused livers from apo E-deficient mice was 50% lower than production by livers from control mice. Lipid composition of nascent VLDL particles isolated from the perfusate was similar for both groups. (c) Mass VLDL-TG secretion by cultured apo E-deficient hepatocytes was reduced by 23% compared with control values in serum-free medium, and by 61% in the presence of oleate in medium (0. 75 mM) to stimulate lipogenesis. Electron microscopic evaluation revealed a smaller average size for VLDL particles produced by apo E-deficient cells compared with control cells in the presence of oleate (38 and 49 nm, respectively). In short-term labeling studies, apo E-deficient and control cells showed a similar time-dependent accumulation of [3H]TG formed from [3H]glycerol, yet secretion of newly synthesized VLDL-associated [3H]TG by apo E-deficient cells was reduced by 60 and 73% in the absence and presence of oleate, respectively. We conclude that apo E, in addition to its role in lipoprotein clearance, has a physiological function in the VLDL assembly-secretion cascade.

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Section: Discussionmentioning

confidence: 99%

Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes.

Kuipers¹,

Jong²,

Lin³

et al. 1997

J. Clin. Invest.

157

136

View full text Add to dashboard Cite

show abstract

“…The liver secretes VLDL particles that are precursors of VLDL remnants, which subsequently may be transformed into IDL and LDL. 10 This cascade occurs as the result of the actions of lipoprotein lipase and hepatic lipase. However, all apoB-containing particles are significantly enriched while circulating in the plasma by the action of the cholesteryl ester transfer protein, which transfers cholesterol, in the form of its ester, from HDL to these particles.…”

Section: In Vivo Metabolism Of Atherogenic Lipoproteinsmentioning

confidence: 99%

New dimension of statin action on apoB atherogenicity

Chapman¹,

McTaggart²

2003

Clin Cardiol

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Newer, more effective statins are powerful agents for reducing elevated levels of low‐density lipoprotein (LDL) cholesterol and thereby lowering the risk of coronary heart disease (CHD) and related adverse events. Although LDL remains the primary target of therapy for reducing CHD risk, increased interest is focusing on apolipoprotein B (apoB)‐containing lipoprotein subfractions—particularly very‐low‐density lipoprotein (VLDL), VLDL remnants, and intermediate‐density lipoproteins (IDL)—as secondary targets of therapy. Elevated apoB is known to be an important risk factor for CHD, and dysregulation of the metabolism of apoB‐containing lipoproteins is involved in the progression of atherosclerosis. Statins reduce circulating concentrations of atherogenic apoB‐containing lipoproteins by decreasing the production of VLDL in the liver and, thus, the production of VLDL remnants and LDL. Statins also increase the clearance of these particles through upregulation of LDL receptors in the liver. Efforts to develop statins with enhanced lipid‐modifying properties are ongoing. The optimal statin would offer a high degree of inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase, a prolonged duration of action, hepatic selectivity for maximal upregulation of LDL receptors, and a low potential for drug–drug interactions. Recent studies have shown that rosuvastatin, a new agent in this class, demonstrates these qualities. Rosuvastatin is a highly effective inhibitor of HMG‐CoA reductase, is relatively nonlipophilic, has a half‐life of approximately 20 h, exhibits hepatic selectivity, has little systemic availability, and has a low potential for drug–drug interactions because of its limited degree of metabolism by the cytochrome P‐450 system. A recent double‐blind, crossover study revealed that treatment with rosuvastatin resulted in marked reductions in apoB‐containing lipoproteins in patients with type IIa or IIb dyslipidemia. By reducing the number of atherogenic lipoprotein particles, rosuvastatin decreases the atherosclerotic burden in hyperlipidemic patients at high risk for CHD and related adverse outcomes.

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“…ApoA-1 is the main component of HDL, which is critical for lipid metabolism and inflammation. Apo B is also synthesized by the liver and is the main structural protein of LDL-CHOL, accounting for about 97% of the total protein content of LDL-CHOL ( 15 ). It has been proposed that the products derived from lipoprotein-peroxide interactions could contribute to mutagenicity and carcinogenicity in cells ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Lipid profile as a novel prognostic predictor for patients with acute myeloid leukemia

et al. 2023

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PurposeThis study investigated the relationship between serum lipid levels and clinical outcomes in acute myeloid leukemia (AML) by establishing a predictive risk classification model.MethodA total of 214 AML patients who were pathologically diagnosed and treated with standard induction chemotherapy at Sun Yat-Sen University Cancer Center were included. The patients were randomly divided into the training (n = 107) and validation (n=107) cohorts. Univariate and multivariate Cox analyses were used to assess the value of triglyceride (TG), Apolipoprotein B (Apo B), Apo Apolipoprotein A-I (Apo A-I), cholesterol (CHO), and high-density lipoprotein (HDL) as prognostic factors for AML.ResultsAfter a series of data analyses, a five-factor model was established to divide the patients into high- and low-risk groups. Kaplan-Meier survival analysis showed that the high-risk group had a poor prognosis (P<0.05). The area under the curve of the novel model for five-year OS was 0.737. A nomogram was constructed to integrate the model with age and the 2017 ELN cytogenetic classification, with the merged model showing improved accuracy with an area under the curve of 0.987 for five-year OS.ConclusionA novel model was constructed using a combination of the serum lipid profile and clinical characteristics of AML patients to enhance the predictive accuracy of clinical outcomes. The nomogram used the lipid profile which is routinely tested in clinical blood biochemistry and showed both specific prognostic and therapeutic potential.

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Factors affecting the regulation of apo b secretion by liver cells

Cited by 7 publications

References 147 publications

Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes.

Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes.

New dimension of statin action on apoB atherogenicity

Lipid profile as a novel prognostic predictor for patients with acute myeloid leukemia

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