Overloading of differentiated Caco-2 cells during lipid transcytosis induces glycosylation mistakes in the Golgi complex

Denisova, Galina N.; Dimov, Ivan; Zaitseva, Anna V.; Artiux, Linard J.; Mirоnоv, Alexander A.; Карелина, Наталья Рафаиловна

doi:10.32604/biocell.2021.014233

Cited by 9 publications

(22 citation statements)

References 71 publications

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“…When such chylomicrons pass through the overloaded Golgi complex (a cellular organelle where a long chain of polysaccharides, like starch or glycogen, is attached to proteins for export) glycosylation (attachment of such chains) of apoproteins is disrupted. Glycosylation errors lead to autoantigens, to which the body responds by producing autoantibodies [62].…”

Section: Historymentioning

confidence: 99%

“…We studied the function of the Golgi apparatus [71], and then checked how the lipid overload of enterocytes affects the structure and chemical composition of chylomicrons [60]. Further, it was proved that enterocyte overload can stimulate the synthesis of polysaccharide autoantigens [62].…”

Section: Our Scientific Discoveriesmentioning

confidence: 99%

“…Lipid transcytosis is impaired when enterocytes are overloaded with lipids, chylomicrons are increased in size [60]. They have glycosylation defects leading to the formation of autoantibodies [62]. When enterocytes are overloaded with lipids, the sialylation of apoproteins and lipids is disturbed and the short branches at the ends of polysaccharide chains are formed from monosaccharides, which can cause auto-antibodies to form.…”

Section: Role Of Overloading Of Enterocytes With Lipids In the Format...mentioning

confidence: 99%

“…It is the sialic acids that shield the short forks of the polysaccharide chains to which the autoantibodies are produced. These enlarged ChMs have few sialic acids at the ends of their polysaccharide chains attached to ApoB [62]. Both small and large lipid particles are actively absorbed from the interstitial space into the lymphatic capillary lumen via the intra-wall valve.…”

Section: Role Of Overloading Of Enterocytes With Lipids In the Format...mentioning

confidence: 99%

“…It turned out that when enterocytes are overloaded with fats, the process of lipid transcytosis through enterocytes is disrupted, lipid droplets associated with ER appear, ChMs become larger and their level of sialylation, sitting on the binding of the corresponding lectins, decreases. Moreover, such overload leads to the synthesis of polysaccharide antigens on apo-proteins, which are not formed normally and, as a consequence, apparently causes the synthesis of auto-antibodies [62].…”

Section: The Role Of Improper Nutritionmentioning

confidence: 99%

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Opinion: On the Way towards the New Paradigm of Atherosclerosis

Mirоnоv

Beznoussenko

2022

IJMS

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Atherosclerosis is a multicausal disease characterized by the formation of cholesterol-containing plaque in the pronounced intima nearest to the heart’s elastic-type arteries that have high levels of blood circulation. Plaques are formed due to arterial pressure-induced damage to the endothelium in areas of turbulent blood flow. It is found in the majority of the Western population, including young people. This denies the monogenic mechanism of atherogenesis. In 1988, Orekhov et al. and Kawai et al. discovered that the presence of atherogenic (modified, including oxidized ones) LDLs is necessary for atherogenesis. On the basis of our discovery, suggesting that the overloading of enterocytes with lipids could lead to the formation of modified LDLs, we proposed a new hypothesis explaining the main factors of atherogenesis. Indeed, when endothelial cells are damaged and then pass through the G2 phase of their cell cycle they secrete proteins into their basement membrane. This leads to thickening of the basement membrane and increases its affinity to LDL especially for modified ones. When the enterocyte transcytosis pathway is overloaded with fat, very large chylomicrons are formed, which have few sialic acids, circulate in the blood for a long time, undergo oxidation, and can induce the production of autoantibodies. It is the sialic acids that shield the short forks of the polysaccharide chains to which autoantibodies are produced. Here, these data are evaluated from the point of view of our new model.

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Section: Historymentioning

confidence: 99%

Section: Our Scientific Discoveriesmentioning

confidence: 99%

Section: Role Of Overloading Of Enterocytes With Lipids In the Format...mentioning

confidence: 99%

Section: Role Of Overloading Of Enterocytes With Lipids In the Format...mentioning

confidence: 99%

Section: The Role Of Improper Nutritionmentioning

confidence: 99%

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Opinion: On the Way towards the New Paradigm of Atherosclerosis

Mirоnоv

Beznoussenko

2022

IJMS

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Algorithm for Modern Electron Microscopic Examination of the Golgi Complex

Mirоnоv¹,

Beznoussenko²

2022

Methods in Molecular Biology

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Role of Endothelial Regeneration and Overloading of Enterocytes with Lipids in Capturing of Lipoproteins by Basement Membrane of Rat Aortic Endothelium

et al. 2022

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Atherosclerosis is a complex non-monogenic disease related to endothelial damage in elastic-type arteries and incorrect feeding. Here, using cryodamage of endothelial cells (ECs) of rat abdominal aorta, we examined the role of the EC basement membrane (BM) for re-endothelization endothelial regeneration and its ability to capture low density lipoproteins (LDLs). Regeneration of endothelium induced thickening of the ECBM. Secretion of the BM components occurred in the G2-phase. Multiple regenerations, as well as arterial hypertension and aging, also led to the thickening of the BM. Under these conditions, the speed of re-endothelialization increased. The thick BM captured more LDLs. LDLs formed after overloading of rats with lipids acquired higher affinity to the BM, presumably due to the prolonged transport of chylomicrons through neuraminidase-positive endo-lysosomes. These data provide new molecular and cellular mechanisms of atherogenesis.

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Overloading of differentiated Caco-2 cells during lipid transcytosis induces glycosylation mistakes in the Golgi complex

Cited by 9 publications

References 71 publications

Opinion: On the Way towards the New Paradigm of Atherosclerosis

Opinion: On the Way towards the New Paradigm of Atherosclerosis

Algorithm for Modern Electron Microscopic Examination of the Golgi Complex

Role of Endothelial Regeneration and Overloading of Enterocytes with Lipids in Capturing of Lipoproteins by Basement Membrane of Rat Aortic Endothelium

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