Effects of Platelet-Activating Factor, Tumor Necrosis Factor, and Interleukin-1α on the Expression of Apolipoprotein M in HepG2 Cells

Xu, N.; Zhang, Xiaoying; Dong, Xuan; Ekström, Ulf; Ye, Qing; Nilsson‐Ehle, Peter

doi:10.1006/bbrc.2002.6755

Cited by 47 publications

(28 citation statements)

References 32 publications

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“…Previous cell-based studies have demonstrated that cytokines such as interleukin-1␣, tumor necrosis factor and transforming growth factor-␤, which are secreted from these leukocyte subsets, downregulate apolipoprotein M, a major protein component of HDL-C (23,24). Thus, the increased counts of the leukocyte subsets may directly reduce HDL-C. Longitudinal studies are needed to examine the causal association between leukocyte subset counts and HDL-C.…”

Section: Discussionmentioning

confidence: 99%

Associations between Leukocyte Counts and Cardiovascular Disease Risk Factors in Apparently Healthy Japanese Men

Mochizuki

Miyauchi

Misaki

et al. 2012

J Nutr Sci Vitaminol

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Summary Increased leukocyte counts, particularly white blood cell and neutrophil counts, are reportedly associated with increased incidence of cardiovascular diseases (CVD) and mortality in subjects with acute and moderate coronary diseases. However, few reports have determined the associations between leukocyte subset (i.e., white blood cells, neutrophils, monocytes, lymphocytes, basophils and eosinophils) counts and CVD risk factors. In this study, we examined the associations between leukocyte subset counts and CVD risk factors in apparently healthy Japanese men. We conducted a cross-sectional study of men who participated in health checkups, and selected those who were not being treated for metabolic diseases. We determined associations between leukocyte subset counts and CVD risk factors by multivariate linear regression (MLR) analysis and analysis of covariance (ANCOVA). Overall, 3,576 subjects aged 49.3 Ϯ 5.75 (range, 40-59) y were recruited. MLR and ANCOVA showed that white blood cell, neutrophil, monocyte counts are associated with decreased high-density lipoprotein cholesterol (HDL-C) and increased C-reactive protein levels, the lymphocyte count is positively associated with lipid abnormalities (i.e., decreased HDL-C, increased low-density lipoprotein cholesterol and increased triacylglycerol (TG)), and the basophil count is associated with increased TG and liver injury marker levels (i.e., alanine aminotransferase). Our results in this study demonstrated that leukocyte subset counts showed differential associations with CVD risk factors in apparently healthy Japanese men.

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Section: Discussionmentioning

confidence: 99%

Associations between Leukocyte Counts and Cardiovascular Disease Risk Factors in Apparently Healthy Japanese Men

Mochizuki

Miyauchi

Misaki

et al. 2012

J Nutr Sci Vitaminol

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“…Previous studies have demonstrated that expression of apoM is regulated by certain cytokines and nuclear factors, including platelet activating factor (PAF), leptin, transforming growth factor-β (TGF-β), epidermal growth factor (EGF), hepatic growth factor (HGF), liver X receptor agonist, and hepatocyte nuclear factor-1α , either in vivo or in vitro [11][12][13][14][15][16][17][18], whereas it is not influenced by ACTH, tumor necrosis factor (TNF-α) or interleukin-1alpha (IL-1α) in cell cultures [12,19]. The impact of apoM on cholesterol and lipoprotein metabolism has been investigated mainly in genetically modified mice.…”

Section: Discussionmentioning

confidence: 99%

Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor

Jiang¹,

Shi²,

Zhang³

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAI and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAI in HepG2 cell cultures in a dose-and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist. In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor.

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“…They elucidated the molecular mechanism by which apoM affects HDL particle size and to exploit a possible new pathway for therapeutic strategies aiming to reduce the development or progression of atherosclerosis [4]. ApoM mRNA levels could be regulated by many intracellular and extracellular factors, including platelet activating factor (PAF), insulin, leptin, transforming growth factor-beta (TGF-β), epidermal growth factor (EGF), hepatic growth factor (HGF), etc., although the function of apoM is unknown yet [5,6,7,8,9,10,11]. Further investigating the regulation of hepatic apoM expression may explore the pathophysiological functions of apoM in vivo.…”

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confidence: 99%

“…Further investigating the regulation of hepatic apoM expression may explore the pathophysiological functions of apoM in vivo. 5 Liver X receptor (LXR) was initially identified as orphan member of the nuclear receptor superfamily that forms obligate heterodimers with retinoid X receptor (RXR) [12]. LXR-RXR can be activated by the endogenous oxysterols and by synthetic agonists such as T0901317 and GW3965 [13,14].…”

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confidence: 99%

ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells

Wang

Liu

et al. 2012

Biochemical and Biophysical Research Communications

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We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoAI, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homologue-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet.The detailed mechanism needs further investigation. 4Keywords: ATP-Binding cassette transporters; Apolipoprotein M; Liver Receptor Homolog-1; Liver X receptor Apolipoprotein M (apoM), one of the most recently discovered plasma apolipoproteins, is mainly associated with high density lipoproteins (HDL), with only a small proportion located in low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles [1]. Human apoM is exclusively expressed in the hepatocytes in liver and tubular epithelial cell in kidney, and small amounts were also found in fetal liver and fetal kidney [2]. Luo, et al.,[3] demonstrated that apoM could also be abundantly expressed in human colorectal tissues, although the pathophysiological importance of this expression and if it could influence plasma apoM pool are unknown. Wolfrum, et al., [4] demonstrated that apoM, by influencing preβ-HDL formation, being an important regulator of HDL metabolism in vivo, which could influence cholesterol efflux and the susceptibility of atherosclerosis. They elucidated the molecular mechanism by which apoM affects HDL particle size and to exploit a possible new pathway for therapeutic strategies aiming to reduce the development or progression of atherosclerosis [4]. ApoM mRNA levels could be regulated by many intracellular and extracellular factors, including platelet activating factor (PAF), insulin, leptin, transforming growth factor-beta (TGF-β), epidermal growth factor (EGF), hepatic growth factor (HGF), etc., although the function of apoM is un...

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Effects of Platelet-Activating Factor, Tumor Necrosis Factor, and Interleukin-1α on the Expression of Apolipoprotein M in HepG2 Cells

Cited by 47 publications

References 32 publications

Associations between Leukocyte Counts and Cardiovascular Disease Risk Factors in Apparently Healthy Japanese Men

Associations between Leukocyte Counts and Cardiovascular Disease Risk Factors in Apparently Healthy Japanese Men

Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor

ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells

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