Sulfur- and Acyl Chain-Dependent Influence of 2-Methoxy-Lysophosphatidylcholine Analogues on β Pancreatic Cells

Title:Sulfur- and Acyl Chain-Dependent Influence of 2-Methoxy-Lysophosphatidylcholine Analogues on β Pancreatic Cells

Volume: 15 Issue: 23

Author(s): Anna Drzazga, Anna Ciesielska and Edyta Gendaszewska-Darmach

Affiliation:

Keywords: βTC-3 pancreatic cells, Calcium flux, Cytotoxicity, Insulin secretion, Lysophosphatidylcholine (LPC), Membrane permeabilization.

Abstract: Nutrient-induced increase in intracellular Ca²⁺ concentration ([Ca²⁺]i) is one of the key mechanisms responsible for insulin release from pancreatic islet β cells. Lysophosphatidylcholine (LPC) was demonstrated to induce insulin secretion from β cells, activate glucose uptake and effectively lower blood glucose levels in mouse models of type 1 and 2 diabetes mellitus. The article hereby presents the results of a characterization of 2-OMe-LPC sulfur analogues with defined acyl residues in terms of their effect on intracellular Ca²⁺ concentration and cellular membrane integrity in the murine βTC-3 cell model. Active LPC series that could induce calcium flux in βTC-3 cell model include unmodified LPC 12:0, 14:0, 16:0, and 18:0 as well as phosphorothioate analogues of LPC 12:0, 14:0 and 16:0. However, in the case of species bearing mirystoyl and palmitoyl residues [Ca²⁺]i was associated with membrane permeabilization as demonstrated by propidium iodide incorporation and lactate dehydrogenase release. LPC 12:0 (both unmodified and a sulfurcontaining counterpart) and unmodified LPC 18:0 did not demonstrate membrane disruption but acted as calcium inducers. Interestingly, no stimulation of calcium flux or membrane disruption was observed in the case of LPC analogues with two sulfur atoms introduced into a phosphate group. Experiments with nitrendipine and NiCl₂ blocking voltage-dependent calcium channels and the general calcium influx, respectively, revealed remarkably that the compounds studied were involved in different signaling mechanisms while administered to the cell culture, which is clearly related to their chemical structure, both acyl chain and modification dependently.

Cite this article as:

Drzazga Anna, Ciesielska Anna and Gendaszewska-Darmach Edyta, Sulfur- and Acyl Chain-Dependent Influence of 2-Methoxy-Lysophosphatidylcholine Analogues on β Pancreatic Cells, Current Topics in Medicinal Chemistry 2015; 15 (23) . https://dx.doi.org/10.2174/1568026615666150619141239