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.

Publication DOI: https://doi.org/10.1016/j.abb.2014.02.013
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > School of Optometry > Optometry & Vision Science Research Group (OVSRG)
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: 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
Uncontrolled Keywords: phosphatidylcholine,hypochlorous acid,apoptosis,Redox imbalance,atherosclerosis
Publication ISSN: 1096-0384
Last Modified: 10 Oct 2024 07:13
Date Deposited: 10 Apr 2014 10:31
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2014-04-15
Published Online Date: 2014-03-04
Authors: Robaszkiewicz, Agnieszka
Bartosz, Grzegorz
Pitt, Andrew R. (ORCID Profile 0000-0003-3619-6503)
Thakker, Alpesh
Armstrong, Richard A. (ORCID Profile 0000-0002-5046-3199)
Spickett, Corinne M. (ORCID Profile 0000-0003-4054-9279)
Soszyński, Mirosław

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