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 journalArticle

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.
LanguageEnglish
Pages1-10
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume548
Early online date4 Mar 2014
DOIs
Publication statusPublished - 15 Apr 2014

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Human Umbilical Vein Endothelial Cells
Phosphatidylcholines
Oxidation-Reduction
Caspase 7
Phospholipids
Cells
Apoptosis
Caspase 3
Chlorohydrins
Cytotoxicity
Cell Count
Hypochlorous Acid
Cell Cycle Checkpoints
Cell Extracts
Oxidation
Glutathione
Endothelial cells
Cell proliferation
Biological systems
Phosphotransferases

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

Cite this

Robaszkiewicz, Agnieszka ; Bartosz, Grzegorz ; Pitt, Andrew R. ; Thakker, Alpesh ; Armstrong, Richard A. ; Spickett, Corinne M. ; Soszyński, Mirosław. / HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells. In: Archives of Biochemistry and Biophysics. 2014 ; Vol. 548. pp. 1-10.
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HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells. / Robaszkiewicz, Agnieszka; Bartosz, Grzegorz; Pitt, Andrew R.; Thakker, Alpesh; Armstrong, Richard A.; Spickett, Corinne M.; Soszyński, Mirosław.

In: Archives of Biochemistry and Biophysics, Vol. 548, 15.04.2014, p. 1-10.

Research output: Contribution to journalArticle

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