Post-transcriptional regulation of apoC-I synthesis and secretion in human HepG2 cells

Bouchard, Catherine; Dubuc, Geneviève; Davignon, Jean; Bernier, Lise; Cohn, Jeffrey S.

doi:10.1016/j.atherosclerosis.2004.09.014

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…VLDL apoC-I content has been positively correlated with fasting triglyceride concentrations and carotid plaque area (41), whereas HDL-mediated apoC-I transport rates were inversely correlated with plasma triglyceride levels (42). The apparent influence of statin therapy on apoC-I abundance in our study is supported by in vitro findings that statin treatment suppressed hepatocyte secretion of apoC-I (43). Nonetheless, subjects who were not on statin therapy also exhibited decreases in HDL-associated apoC-I, and changes in serum apoC-I have been observed consequent to hormone replacement therapy in women (28).…”

Section: Discussionsupporting

confidence: 84%

Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity

Rubinow

Vaisar

Tang

et al. 2012

Journal of Lipid Research

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The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51–83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5α-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen α chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride. Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men.

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Section: Discussionsupporting

confidence: 84%

Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity

Rubinow

Vaisar

Tang

et al. 2012

Journal of Lipid Research

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“…Overall, although apoC1 gene is expressed in many tissues such as lung, skin, testes, spleen, and adipose tissue, the main sites for its expression are the liver and differentiated macrophages [ 19 , 24 , 29 , 30 ]. In addition to regulation of apoC1 gene expression at the transcriptional level, the secretion of apoC1 protein can also be modulated post-transcriptionally, with a stimulatory effect in the context of increased cholesterol pool, while cellular triglyceride content had no effect [ 31 ].…”

Section: Apoc1 Structure and Genementioning

confidence: 99%

Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review

Rouland

Masson

Lagrost

et al. 2022

Cardiovasc Diabetol

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Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes.

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“…Thus, a proteomic analysis on a subgroup of the Leipziger LIFE-Heart Study revealed a decrease in apoC1 level upon statin treatment [141]. An important point to stress is that there is no direct correlation between the level of mRNA and the secreted protein, since the latter is post-transcriptionally regulated, in a cholesterol-dependent manner, at least in vitro in HepG2 cells [142]. In THP-1 macrophages, the observed reduction of mRNA correlated with the level of secreted protein upon treatment with atorvastatin, but not with cerivastatin [143].…”

Section: Apoc1 In Pathologymentioning

confidence: 99%

Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond

Fuior¹,

Gafencu²

2019

IJMS

129

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Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein classes. These interactions occur via amphipathic helix motifs, as demonstrated by biophysical studies on the wild-type polypeptide and representative mutants. Apolipoprotein C1 acts on lipoprotein receptors by inhibiting binding mediated by apolipoprotein E, and modulating the activities of several enzymes. Thus, apoC1 downregulates lipoprotein lipase, hepatic lipase, phospholipase A2, cholesterylester transfer protein, and activates lecithin-cholesterol acyl transferase. By controlling the plasma levels of lipids, apoC1 relates directly to cardiovascular physiology, but its activity extends beyond, to inflammation and immunity, sepsis, diabetes, cancer, viral infectivity, and—not last—to cognition. Such correlations were established based on studies using transgenic mice, associated in the recent years with GWAS, transcriptomic and proteomic analyses. The presence of a duplicate gene, pseudogene APOC1P, stimulated evolutionary studies and more recently, the regulatory properties of the corresponding non-coding RNA are steadily emerging. Nonetheless, this prototypical apolipoprotein is still underexplored and deserves further research for understanding its physiology and exploiting its therapeutic potential.

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Post-transcriptional regulation of apoC-I synthesis and secretion in human HepG2 cells

Cited by 7 publications

References 51 publications

Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity

Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity

Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review

Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond

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