Effect of osmolarity on LDL binding and internalization in hepatocytes |
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Authors: | Kramer-Guth, Annette Busch, Gillian L. Kaba, Nubia Kristen Schwedler, Susanne Wanner, Christoph Lang, Florian |
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Abstract: | The present study has been performed to elucidate a possiblerole of cell volume in low-density lipoprotein (LDL) binding andinternalization (LDLb+i). Asshown previously, increase of extracellular osmolarity (OSMe) andK+ depletion, both known to shrinkcells, interfere with the formation of clathrin-coated pits and thuswith LDLb+i. On the other hand,alterations of cell volume have been shown to modify lysosomal pH,which is a determinant of LDLb+i.LDLb+i have been estimated fromheparin-releasable (binding) or heparin-insensitive (internalization)uptake of 125I-labeled LDL. OSMewas modified by alterations of extracellular concentrations of ions,glucose, urea, or raffinose. When OSMe was altered by varying NaClconcentrations, LDLb+i decreased (by 0.5 ± 0.1%/mM) with increasing OSMe andLDLb+i increased (by 1.2 ± 0.1%/mM) with decreasing OSMe, an effect mainly due to alteredaffinity; the estimated dissociation constant amounted to 20.6, 48.6, and 131.6 µg/ml at 219, 293, and 435 mosM, respectively. A 25%increase of OSMe increased cytosolic (by 0.46 ± 0.03) and decreasedlysosomal (by 0.14 ± 0.02) pH. Conversely, a 25% decrease of OSMedecreased cytosolic (by 0.28 ± 0.02) and increased lysosomal (by0.17 ± 0.02) pH. Partial replacement of extracellularNa+ withK+ had little effect onLDLb+i, although it swelledhepatocytes and increased lysosomal and cytosolic pH. Hypertonicglucose, urea, or raffinose did not exert similar effects despite ashrinking effect of hypertonic raffinose. Monensin, which completelydissipates lysosomal acidity, virtually abolishedLDLb+i. In conclusion, theobservations reveal a significant effect of ionic strength onLDLb+i. The effect is, however,not likely to be mediated by alterations of cell volume or alterationsof lysosomal pH. |
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