title: HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells.
abstract: Electrophilic attack of hypochlorous acid on unsaturated bonds of fatty acyl chains is known to result mostly in chlorinated products that show cytotoxicity to some cell lines and were found in biological systems exposed to HOCl. This study aimed to investigate more deeply the products and the mechanism underlying cytotoxicity of phospholipid-HOCl oxidation products, synthesized by the reaction of HOCl with 1-stearoyl-2-oleoyl-, 1-stearoyl-2-linoleoyl-, and 1-stearoyl-2-arachidonyl-phosphatidylcholine. Phospholipid chlorohydrins were found to be the most abundant among obtained products. HOCl-modified lipids were cytotoxic towards HUVEC-ST (endothelial cells), leading to a decrease of mitochondrial potential and an increase in the number of apoptotic cells. These effects were accompanied by an increase of the level of active caspase-3 and caspase-7, while the caspase-3/-7 inhibitor Ac-DEVD-CHO dramatically decreased the number of apoptotic cells. Phospholipid-HOCl oxidation products were shown to affect cell proliferation by a concentration-dependent cell cycle arrest in the G0/G1 phase and activating redox sensitive p38 kinase. The redox imbalance observed in HUVEC-ST cells exposed to modified phosphatidylcholines was accompanied by an increase in ROS level, and a decrease in glutathione content and antioxidant capacity of cell extracts.
authors.affiliation: Department of Environmental Pollution Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland. Electronic address: robaszkiewicz.agnieszkaz@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Robaszkiewicz
authors.affiliation: Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland; Department of Biochemistry and Cell Biology, University of Rzeszów, St. Pigonia 6, 35-959 Rzeszów, Poland. Electronic address: grzegorz.bartosz@gmail.com.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bartosz
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: a.r.pitt@aston.ac.uk.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pitt
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: thakkera@aston.ac.uk.
authors.forename: Alpesh
authors.initials: A
authors.lastname: Thakker
authors.affiliation: Ophthalmic Research Group, School of Life and Health Sciences, School of Optometry, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: r.a.armstrong@aston.ac.uk.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Armstrong
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: c.m.spickett@aston.ac.uk.
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Spickett
authors.affiliation: Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland. Electronic address: sosmirek@biol.uni.lodz.pl.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Soszyński
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002728:Chlorohydrins / Q000737:chemistry* / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D002728:Chlorohydrins; D010743:Phospholipids; D006997:Hypochlorous Acid; D053148:Caspase 3; D053179:Caspase 7
keywords: Apoptosis; Atherosclerosis; Hypochlorous acid; Phosphatidylcholine; Redox imbalance