scholarly journals Stimulation of ABCB4/MDR3 ATPase activity requires an intact phosphatidylcholine lipid

2020 ◽  
Vol 61 (12) ◽  
pp. 1605-1616 ◽  
Author(s):  
Martin Prescher ◽  
Sander H. J. Smits ◽  
Lutz Schmitt
Keyword(s):  
Atpase Activity ◽  
Bile Salts ◽  
Mixed Micelles ◽  
Substrate Selection ◽  
Protective Function ◽  
Canalicular Membrane ◽  
Acyl Chains ◽  
Quantitative Impact ◽  
Detergent Effect

ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates PC-lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so, ABCB4 provides PC lipids for extraction into bile. PC lipids account for 40% of the entire pool of lipids in the canalicular membrane with an unknown distribution over both leaflets. Extracted PC lipids end up in so-called mixed micelles. Mixed micelles are composed of phospholipids, bile salts, and cholesterol. Ninety to ninety-five percent of the phospholipids are members of the PC family, but only a subset of mainly 16.0-18:1 PC and 16:0-18:2 PC variants are present. To elucidate whether ABCB4 is the key discriminator in this enrichment of specific PC lipids, we used in vitro studies to identify crucial determinants in substrate selection. We demonstrate that PC-lipid moieties alone are insufficient for stimulating ABCB4 ATPase activity, and that at least two acyl chains and the backbone itself are required for a productive interaction. The nature of the fatty acids, like length or saturation has a quantitative impact on the ATPase activity. Our data demonstrate a two-step enrichment and protective function of ABCB4 to mitigate the harsh detergent effect of the bile salts, because ABCB4 can translocate more than just the PC-lipid variants found in bile.

Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile.

1979 ◽  
Vol 236 (1) ◽  
pp. E10
Author(s):  
S Binet ◽  
Y Delage ◽  
S Erlinger
Keyword(s):  
Bile Salts ◽  
Mixed Micelle ◽  
Mixed Micelles ◽  
Important Determinant ◽  
Micelle Formation ◽  
Similar Increase ◽  
Mixed Micelle Formation ◽  
Series Of Experiments

To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.

In vitro effect of bile salts on rat liver plasma membrane, lipid fluidity, and ATPase activity

Hepatology ◽  
1981 ◽  
Vol 1 (2) ◽  
pp. 137-145 ◽  
Author(s):  
Bruce F. Scharschmidt ◽  
Emmet B. Keeffe ◽  
Donald A. Vessey ◽  
Nancy M. Blankenship ◽  
Robert K. Ockner
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Rat Liver ◽  
Bile Salts ◽  
Membrane Lipid ◽  
Liver Plasma Membrane ◽  
Plasma Membrane Lipid ◽  
Vitro Effect ◽  
Membrane Lipid Fluidity

Mixed Micelles as Nano Polymer Therapeutics of Docetaxel: Increased In vitro Cytotoxicity and Decreased In vivo Toxicity

2018 ◽  
Vol 15 (4) ◽  
pp. 564-575 ◽  
Author(s):  
Arehalli S. Manjappa ◽  
Popat S. Kumbhar ◽  
Prajakta S. Khopade ◽  
Ajit B. Patil ◽  
John I. Disouza
Keyword(s):  
Mixed Micelles ◽  
In Vitro Cytotoxicity ◽  
Polymer Therapeutics ◽  
In Vivo Toxicity

scholarly journals Dissection of Swa2p/Auxilin Domain Requirements for Cochaperoning Hsp70 Clathrin-uncoating Activity In Vivo

2006 ◽  
Vol 17 (7) ◽  
pp. 3281-3290 ◽  
Author(s):  
Jing Xiao ◽  
Leslie S. Kim ◽  
Todd R. Graham
Keyword(s):  
Atpase Activity ◽  
Point Mutation ◽  
Mutational Analysis ◽  
Weak Interactions ◽  
Tetratricopeptide Repeat ◽  
Uba Domain ◽  
J Domain ◽  
Tpr Domain

The auxilin family of J-domain proteins load Hsp70 onto clathrin-coated vesicles (CCVs) to drive uncoating. In vitro, auxilin function requires its ability to bind clathrin and stimulate Hsp70 ATPase activity via its J-domain. To test these requirements in vivo, we performed a mutational analysis of Swa2p, the yeast auxilin ortholog. Swa2p is a modular protein with three N-terminal clathrin-binding (CB) motifs, a ubiquitin association (UBA) domain, a tetratricopeptide repeat (TPR) domain, and a C-terminal J-domain. In vitro, clathrin binding is mediated by multiple weak interactions, but a Swa2p truncation lacking two CB motifs and the UBA domain retains nearly full function in vivo. Deletion of all CB motifs strongly abrogates clathrin disassembly but does not eliminate Swa2p function in vivo. Surprisingly, mutation of the invariant HPD motif within the J-domain to AAA only partially affects Swa2p function. Similarly, a TPR point mutation (G388R) causes a modest phenotype. However, Swa2p function is abolished when these TPR and J mutations are combined. The TPR and J-domains are not functionally redundant because deletion of either domain renders Swa2p nonfunctional. These data suggest that the TPR and J-domains collaborate in a bipartite interaction with Hsp70 to regulate its activity in clathrin disassembly.

scholarly journals Gastroprotective Value of Berries: Evidences from Methanolic Extracts of Morus nigra and Rubus niveus Fruits

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Luciane Angela Nottar Nesello ◽  
Maria Luisa Maes Lima Beleza ◽  
Marihá Mariot ◽  
Luísa Nathália Bolda Mariano ◽  
Priscila de Souza ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Free Radical Scavenger ◽  
Total Phenolic ◽  
Radical Scavenger ◽  
Lipid Hydroperoxides ◽  
Ulcer Area ◽  
Morus Nigra ◽  
Radical Scavenger Activity ◽  
Scavenger Activity

This study evaluated the gastroprotective value of the methanol extracts from fruits of Morus nigra L. (black mulberry (MEMN)) and Rubus niveus Thunb (raspberry (MERN)). The total phenolic compounds and flavonoids were measured, as well as the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenger activity. The gastroprotective effects of the extracts against 60% ethanol/0.3 M HCl were evaluated in mice. After that, the lipid hydroperoxides and reduced glutathione levels at ulcerated tissue were determined. The effects of extracts on H+/K+-ATPase activity were also verified. The extracts exhibited high contents of polyphenols; however, MERN presented 1.5-fold higher levels. The presence of flavonoids also was confirmed. In addition, MEMN (IC50 = 13.74 μg/mL) and MERN (IC50 = 14.97 μg/mL) scavenged DPPH radical. The MEMN reduced the ulcer area only at 300 mg/kg (p.o.) by 64.06%. Interestingly, MERN decreased the ulcer area in a superior potency (ED50 = 20.88 mg/kg), reducing the ulcer area by 81.86% at 300 mg/kg, and increased the gastric mucin levels. The antioxidant effects of extracts were evidenced by reduced lipoperoxides and increased reduction of glutathione amount in the gastric mucosa. However, MEMN or MERN did not change the H+/K+-ATPase activity. These results confirm that M. nigra and R. niveus are berries with a gastroprotective value by strengthening of gastric protective factors.

scholarly journals Assessment of the Nutritional Value, Techno-Functional, and In Vitro Physiological Properties of Six Edible Insects

Proceedings ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 77
Author(s):  
Yolanda Aguilera ◽  
Miguel Rebollo-Hernanz ◽  
Irene Pastrana ◽  
Vanesa Benitez ◽  
Gerardo Alvarez-Rivera ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Bulk Density ◽  
Bile Salts ◽  
Positive Impact ◽  
Starch Hydrolysis ◽  
Hydration Properties ◽  
Physiological Properties ◽  
Glucose Diffusion ◽  
Foaming Capacity

The objective of this study was to evaluate the nutritional composition, techno-functional, and in vitro physiological properties of flours from six different insect species (mealworm, beetle, caterpillar, ant, locust, and cricket). The chemical composition of insects was evaluated following the standard methods (AOAC). Bulk density, water holding capacity, oil holding capacity, water absorption capacity, swelling capacity, emulsifying activity, foaming capacity, and gelation capacity were measured. In vitro antioxidant capacity was measured by the direct ABTS method. Hypoglycemic (glucose adsorption and the inhibition of α-amylase, glucose diffusion, and starch hydrolysis) and hypolipidemic (cholesterol and bile salts binding and lipase inhibition capacities) were investigated using in vitro methods. Insect flours exhibited a high content of protein (39.4%–58.1%) and fat (17.7%–50.1%) as main components, although the presence of chitin in ant samples was also highlighted. The techno-functional properties showed high oil holding, swelling, and emulsifying capacities in all insect flours analyzed, besides bulk density, hydration properties, and foaming capacity showing average values and no gelation capacity. Insects showed high antioxidant capacity (179–221 mg Trolox equivalents/g). Moreover, these edible insect flours revealed effective hyperglycemic and hyperlipidemic properties. Insect flours inhibited α-amylase activity (47.1%–98.0%) and retarded glucose diffusion (17.2%–29.6%) and starch hydrolysis (18.2%–88.1%). Likewise, they bound cholesterol and bile salts (8.4%–98.6%) and inhibited lipase activity (8.9%–47.1%). Hence, these insect flours might be of great interest to the food industry, being a healthy source of protein, exerting a positive impact on functional food properties, and potentially preventing the development of diseases associated with hyperglycemia and hyperlipidemia.

Hepatocelluar cytoprotection by hydrophilic bile salts is through enhancing canalicular membrane fluidity and packing density

2000 ◽  
Vol 118 (4) ◽  
pp. A1422
Author(s):  
Yasumasa Asamoto ◽  
Susumu Tazuma ◽  
Hidenori Ochi ◽  
Tsuyoshi Kajihara ◽  
Hideyuki Hyougo ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Packing Density ◽  
Bile Salts ◽  
Canalicular Membrane
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