TY - JOUR
T1 - HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells
AU - Robaszkiewicz, Agnieszka
AU - Bartosz, Grzegorz
AU - Pitt, Andrew R.
AU - Thakker, Alpesh
AU - Armstrong, Richard A.
AU - Spickett, Corinne M.
AU - Soszynski, Miroslaw
PY - 2014/4/15
Y1 - 2014/4/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Atherosclerosis
KW - Hypochlorous acid
KW - Phosphatidylcholine
KW - Redox imbalance
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_starter&SrcAuth=WosAPI&KeyUT=WOS:000334975300001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.abb.2014.02.013
DO - 10.1016/j.abb.2014.02.013
M3 - Article
C2 - 24607806
SN - 0003-9861
VL - 548
SP - 1
EP - 10
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -