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. and Soszyński, Mirosław (2014). HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells. Archives of Biochemistry and Biophysics, 548 , pp. 1-10.

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: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Cellular and Molecular Biomedicine
Life & Health Sciences > Biosciences
Life & Health Sciences > Optometry
Life & Health Sciences > Ophthalmic Research Group
Life & Health Sciences > Vision, Hearing and Language
Life & Health Sciences > Clinical and Systems Neuroscience
Life & Health 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
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2014-04-15
Authors: Robaszkiewicz, Agnieszka
Bartosz, Grzegorz
Pitt, Andrew R. ( 0000-0003-3619-6503)
Thakker, Alpesh
Armstrong, Richard A. ( 0000-0002-5046-3199)
Spickett, Corinne M. ( 0000-0003-4054-9279)
Soszyński, Mirosław

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