Biosynthesis and excretion of gangliosides by the isolated perfused rat liver

Senn, Hans-Jürgen; Sellin, Susanne; Fitzke, Edith; Stehlé, Thomas; Häussinger, Dieter; Wieland, Heinrich; Gerok, W.

doi:10.1111/j.1432-1033.1992.tb16845.x

Cited by 15 publications

(4 citation statements)

References 24 publications

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“…Although we presently do not have enough evidence to indicate the means by which hydroxylated GM3 molecular species are enriched in the individuals of VFA with metabolic disease, the observation that hydroxylated GM3 molecular species are far more abundant than hydroxylated ceramide molecular species seems to point to the mechanism of direct hydroxylation. It is interesting to note that a linear correlation has been reported between GM3 molecular species containing hydroxylated acyl chains and aging in the human liver [ 30 ], the site of excretion of gangliosides into mammalian sera [ 25 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome

Veillon

Matsuyama

et al. 2015

PLoS ONE

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Serum GM3 molecular species were quantified in 125 Japanese residents using tandem mass spectrometry multiple reaction monitoring. Individuals were categorized by the presence or absence of metabolic disease risk factors including visceral fat accumulation, hyperglycemia and dyslipidemia. A total of 23 GM3 molecular species were measured, of these, eight were found to be significantly elevated in individuals with visceral fat accumulation and metabolic disease, defined as the presence of hyperglycemia and dyslipidemia. All of the GM3 molecular species were composed of the sphingoid base sphingosine (d18:1 (Δ4)) and, interestingly, six of the eight elevated GM3 molecular species contained a hydroxylated ceramide moiety. The hydroxylated GM3 species were, in order of decreasing abundance, d18:1-h24:0 ≈ d18:1-h24:1 > d18:1-h22:0 » d18:1-h20:0 > d18:1-h21:0 > d18:1-h18:1. Univariate and multiple linear regression analyses were conducted using a number of clinical health variables associated with obesity, type 2 diabetes, metabolic disease, atherosclerosis and hypertension. GM3(d18:1-h24:1) was identified as the best candidate for metabolic screening, proving to be significantly correlated with intima-media thickness, used for the detection of atherosclerotic disease in humans, and a number of metabolic disease risk factors including autotaxin, LDL-c and homeostatic model assessment insulin resistance (HOMA-IR).

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Section: Discussionmentioning

confidence: 99%

Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome

Veillon

Matsuyama

et al. 2015

PLoS ONE

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“…The composition of gangliosides in liver tissues not only shows species-specific patterns, but also varies among different strains of inbred animals (Nilsson and Svennerholm, 1982;Ghidoni et al, 1983;Kasai et al, 1993). Metabolic studies of liver gangliosides have also been conducted using in vivo or organ-perfusion systems (Trinchera et al, 1990a, b;Senn et al, 1992) and in vitro cultures of isolated hepatocytes with radiolabeled precursors (Rump et al, 1986;Mesaric and Decker, 1990;Merrill et al, 1995). While it has been demonstrated that the metabolism of hepatic gangliosides is influenced by hormones (Phillips et al, 1985) or aging (Phillips et al, 1985;Nakamura et al, 1988), information on the regulatory factors for the expression of gangliosides in the liver remains limited.…”

Section: Introductionmentioning

confidence: 98%

Growth- and Development-Dependent Expression of Gangliosides in Rat Hepatocytes and Liver Tissues

Sugiyama¹,

Saito²

1999

Biological Chemistry

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Expression of gangliosides in the liver was examined in primary cultures of hepatocytes from adult rats and liver tissues from rats of different ages. Hepatocytes were isolated from 7-week-old rat liver and cultured in L-15 medium containing insulin, dexamethasone and 10% fetal bovine serum. Hepatocytes proliferated only on the first day, and then ceased proliferation. The content of GD3 and GD1a increased during the period of active proliferation and reached a nearly constant level, whereas GM1, GD1b, GT1b, and GQ1b gradually increased throughout culture. Addition of EGF to the culture medium caused significant increases in the content of GD3, and to a lesser degree of GM3, but exhibited little effect on the expression of other ganglioside species. The specific induction of GD3 and GM3 expression by EGF was reproduced under serum-free conditions, despite the lack of hepatocyte proliferation. Expression of gangliosides in cultured hepatocytes was also modulated by cell density; higher cell density brought about increased content of GM1, GD1a, GD1b, GT1b, and GQ1b with concomitant reduction of GM3 in cells. The composition of gangliosides in liver tissues demonstrated a unique developmental pattern. GD3 and GD1a were strongly expressed in E-16 embryonic tissue and rapidly decreased with increasing age. GD1b, GT1b, and GQ1b were found only in postnatal liver tissues. These findings suggest that the expression of gangliosides in rat hepatocytes and liver tissues are regulated by growth- and development-dependent factors.

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“…They have sphingosine‐fatty acid amide linkage and sialic acid and thus, gangliosides are sialic acid or N ‐acetylneuraminic acid (NeuAc)‐containing GSLs [Tettamanti, ; Chung et al, ; Jin et al, ; Kim et al, ; Ha et al, ]. Plasma free gangliosides or lipoprotein‐assembled glycolipids are mainly synthesized from liver and secreted to serum [Senn et al, ]. Various gangliosides have been structurally isolated from plasma in the forms of free or lipoprotein‐associated assembly [Senn et al, ; Rebba and Portoukalian, ; Tettamanti, ].…”

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confidence: 99%

Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells

et al. 2017

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Some sialic acid-containing glycolipids are known to regulate development of atherosclerosis with accumulated plasma apolipoprotein B-100 (Apo-B)-containing lipoproteins, because Apo-B as an atherogenic apolipoprotein is assembled mainly in VLDL and LDL. Previously, we have elucidated that disialyl GD3 promotes the microsomal triglyceride transfer protein (MTP) gene expression and secretion of triglyceride (TG)-assembled ApoB, claiming the GD3 role in ApoB lipoprotein secretion in liver cells. In the synthetic pathway of gangliosides, GD3 is synthesized by addition of a sialic acid residue to GM3. Thus, there should be some regulatory links between GM3 and GD3. In this study, exogenous and endogenous monosialyl GM3 has been examined how GM3 plays a role in ApoB secretion in Chang liver cells in a view point of MTP and ApoB degradation in the same cells. The level of GM3 ganglioside in the GM3 synthase gene-transfected cells was increased in the cell extract, but not in the medium. In addition, GM3 synthase gene-transfected cells showed a diminished secretion of TG-enriched ApoB with a lower content of TG in the medium. Exogenous GM3 treatment for 24 h exerted a dose dependent inhibitory effect on ApoB secretion together with TG, while a liver-specific albumin was unchanged, indicating that GM3 effect is limited to ApoB secretion. GM3 decreased the mRNA level of MTP gene, too. ApoB protein assembly dysregulated by GM3 indicates the impaired ApoB secretion is caused by a proteasome-dependent pathway. Treatment with small interfering RNAs (siRNAs) decreased ApoB secretion, but GM3-specific antibody did not. These results indicate that plasma membrane associated GM3 inhibits ApoB secretion, lowers development of atherosclerosis by decreasing the secretion of TG-enriched ApoB containing lipoproteins, suggesting that GM3 is an inhibitor of ApoB and TG secretion in liver cells. J. Cell. Biochem. 118: 2168-2181, 2017. © 2017 Wiley Periodicals, Inc.

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Biosynthesis and excretion of gangliosides by the isolated perfused rat liver

Cited by 15 publications

References 24 publications

Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome

Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome

Growth- and Development-Dependent Expression of Gangliosides in Rat Hepatocytes and Liver Tissues

Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells

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