HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

Agnieszka Robaszkiewicz; Grzegorz Bartosz; Andrew R. Pitt; Alpesh Thakker; Richard A. Armstrong; Corinne M. Spickett; Mirosław Soszyński

doi:10.1016/j.abb.2014.02.013

HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

Agnieszka Robaszkiewicz, Grzegorz Bartosz, Andrew R. Pitt, Alpesh Thakker, Richard A. Armstrong, Corinne M. Spickett, Mirosław Soszyński

Research output: Contribution to journal › Article › peer-review

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 G/G 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.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Archives of Biochemistry and Biophysics
Volume	548
Early online date	4 Mar 2014
DOIs	https://doi.org/10.1016/j.abb.2014.02.013
Publication status	Published - 15 Apr 2014

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Archives of biochemistry and biophysics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Robaszkiewicz, A., Bartosz, G., Pitt, A. R., Thakker, A., Armstrong, R. A., Spickett, C. M., & Soszyński, M. (2014). HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells. Archives of biochemistry and biophysics, vol. 548 (2014) DOI http://dx.doi.org/10.1016/j.abb.2014.02.013

Keywords

phosphatidylcholine
hypochlorous acid
apoptosis
Redox imbalance
atherosclerosis

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10.1016/j.abb.2014.02.013

HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance
NOTICE: this is the author’s version of a work that was accepted for publication in Archives of biochemistry and biophysics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Robaszkiewicz, A., Bartosz, G., Pitt, A. R., Thakker, A., Armstrong, R. A., Spickett, C. M., & Soszynski, M. (2014). HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells. Archives of biochemistry and biophysics, vol. 548 (2014) DOI http://dx.doi.org/10.1016/j.abb.2014.02.013
Accepted author manuscript, 1.63 MB

Cite this

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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 G/G 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.",

keywords = "phosphatidylcholine, hypochlorous acid, apoptosis, Redox imbalance, atherosclerosis",

author = "Agnieszka Robaszkiewicz and Grzegorz Bartosz and Pitt, {Andrew R.} and Alpesh Thakker and Armstrong, {Richard A.} and Spickett, {Corinne M.} and Miros{\l}aw Soszy{\'n}ski",

note = "NOTICE: this is the author{\textquoteright}s version of a work that was accepted for publication in Archives of biochemistry and biophysics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Robaszkiewicz, A., Bartosz, G., Pitt, A. R., Thakker, A., Armstrong, R. A., Spickett, C. M., & Soszy{\'n}ski, M. (2014). HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells. Archives of biochemistry and biophysics, vol. 548 (2014) DOI http://dx.doi.org/10.1016/j.abb.2014.02.013",

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AU - Robaszkiewicz, Agnieszka

AU - Bartosz, Grzegorz

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AU - Thakker, Alpesh

AU - Armstrong, Richard A.

AU - Spickett, Corinne M.

AU - Soszyński, Mirosław

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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 G/G 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 G/G 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 - phosphatidylcholine

KW - hypochlorous acid

KW - apoptosis

KW - Redox imbalance

KW - atherosclerosis

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JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

ER -

HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

Abstract

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Keywords

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