title: Sulfur- and acyl chain-dependent influence of 2-methoxy-lysophosphatidylcholine analogues on β pancreatic cells.
abstract: Nutrient-induced increase in intracellular Ca(2+) concentration ([Ca(2+)]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 Ca(2+) 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 [Ca(2+)]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.
authors.forename: Anna
authors.initials: A
authors.lastname: Drzazga
authors.forename: Anna
authors.initials: A
authors.lastname: Ciesielska
authors.affiliation: Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-924 Lodz, Poland. edarmach@wp.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Gendaszewska-Darmach
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000737:chemistry* / Q000494:pharmacology; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D013457:Sulfur Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D015220:Calcium Channels; D007328:Insulin; D008244:Lysophosphatidylcholines; D013457:Sulfur Compounds; D002118:Calcium