Distribution of the LDL receptor within clathrin-coated pits and caveolae in rat and human liver

Ivaturi, Soumya; Wooten, Catherine J.; Nguyen, Maikhanh D.; Ness, Gene C.; Lopez, Dayami

doi:10.1016/j.bbrc.2014.02.019

Cited by 14 publications

(8 citation statements)

References 24 publications

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“…Specific amino acids such as cysteine are involved in post-translational modifications that include oxidation, nitrosylation, or disulfide bond formation [ 140 , 141 ] with electrostatics that have and play important roles in biology such as toxic Aβ oligomer formation. Cysteine residues are important to many protein functions and patulin has been shown to induce cysteine intra and inter molecular crosslinks that effect many cholesterol interacting proteins such as GPCR receptor activation, apo AI-ABCA1 cholesterol dependent efflux, LRP-1 associated LPS/mycotoxin metabolism, LDLr binding of lipoproteins, apo E (E2, E3, E4)/Aβ interactions, and phospholipid transport protein synthesis/secretion that effects apo E-PLTP activity [ 138 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ]. The mycotoxin patulin has been shown to be neurotoxic and in mice patulin has been shown to induce brain damage [ 153 , 154 ].…”

Section: Patulin and Lps Effect Electrostatic Aβ Oligomer Formatiomentioning

confidence: 99%

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Martins

2015

IJMS

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Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration.

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Section: Patulin and Lps Effect Electrostatic Aβ Oligomer Formatiomentioning

confidence: 99%

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Martins

2015

IJMS

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“…3A, monensin treatment resulted in a significant induction (4.44-fold; n=12; p<0.0001) in the binding of LDL to the C3A cells. We also performed binding studies with BODIPY®-LDL followed by detection using flow cytometry as previously described [34] and obtained comparable results (5.33-fold induction by monensin treatment; p=0.0026; n=8; data not shown).…”

Section: Fig 3 Effects Of Monensin On the Binding Of Lipoproteins Tomentioning

confidence: 65%

“…We have previously demonstrated that C3A cells grown in MITO+ medium have more LDL receptors in the clathrin-coated pits than in caveolae and that treating rats with zaragozic acids (ZA), a potent cholesterol biosynthesis inhibitor, increases the distribution of the LDL receptor towards the clathrin-coated pits [34]. Thus, it might be possible that monensin treatment enhanced the distribution of the LDL receptor to clathrin-coated pits explaining the higher binding of LDL, but not of VLDL, to the cells.…”

Section: Discussionmentioning

confidence: 99%

Monensin Enhances the Binding of LDL to Human Hepatocyte-Like C3A Cells without Increasing the Number of LDL Receptors at the Plasma Membrane

2015

American Research Journal of Pharmacy

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The hepatic LDL receptor is the major determinant of plasma LDL levels, and as a result, a greater understanding of the regulatory mechanisms that control LDL receptor expression and function is essential. Herein, we optimized a biotinylation assay that was able to differentiate between cell surface (plasma membrane) and intracellular LDL receptors. We also tested monensin, a chemical that prevents the recycling of the LDL receptors to the cell surface and enhances the number of receptors that can bind and internalize LDL. Herein, it was confirmed the effects of monensin on the ability of the LDL receptor to bind LDL, and demonstrated for the first time, using the biotinylation assay, that monensin did not affect the LDL receptor expression levels at the plasma membrane or inside the cell. This was confirmed using immunocy to chemistry and Western blotting analysis. Monensin treatment may enhance the distribution of the LDL receptor to clathrin-coated pits explaining the higher binding of LDL, but not of VLDL, to the cells. This effect of monensin did not require upregulation of the LDL receptor expression. This indicates that the biotinylation assay described herein, in combination with monensin treatment, could be used in future studies to determine the effects of different treatments/drugs on the plasma membrane distribution/function of the hepatic LDL receptors.

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“…40 Normally, LDL binds specifically to LDLR with high affinity at the cell membrane, the LDL-LDLR complexes cluster into clathrin-coated pits, and are then internalized by clathrin-mediated endocytosis. After being internalized into cytoplasm, LDL-LDLR complexes are transferred into early endosomes, where low pH triggers dissociation of LDL from LDLR.…”

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confidence: 99%

“…The dissociated LDL fuses with lysosomes, and is eventually degraded to CH, lipids, and free amino acids by acidic hydrolases in the endosomes. 19,40,41 In order to investigate whether PTX-CH Emul could mimic the internalization pathway and the fate of LDL, the LDLR-binding assay, endocytosis pathway, and intracellular trafficking of PTX-CH Emul were studied. As shown in the results of the binding assay, FL-PTX-CH had a higher binding affinity to LDLR than FL-DMSO and FL-PTX Emul in MDA-MB-231 cells.…”

mentioning

confidence: 99%

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

Ye¹,

Xia²,

Dong³

et al. 2016

IJN

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There is no effective clinical therapy for triple-negative breast cancers (TNBCs), which have high low-density lipoprotein (LDL) requirements and express relatively high levels of LDL receptors (LDLRs) on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul) was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231) and non-TNBC (MCF7) cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy.

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Distribution of the LDL receptor within clathrin-coated pits and caveolae in rat and human liver

Cited by 14 publications

References 24 publications

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Monensin Enhances the Binding of LDL to Human Hepatocyte-Like C3A Cells without Increasing the Number of LDL Receptors at the Plasma Membrane

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

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Distribution of the LDL receptor within clathrin-coated pits and caveolae in rat and human liver

Cited by 14 publications

References 24 publications

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases

Monensin Enhances the Binding of LDL to Human Hepatocyte-Like C3A Cells without Increasing the Number of LDL Receptors at the Plasma Membrane

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel&ndash;cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

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Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines