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J Cell Physiol. 2010 Nov;225(3):829-36. doi: 10.1002/jcp.22290.

Role of calcium and ROS in cell death induced by polyunsaturated fatty acids in murine thymocytes.

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1
Department of Environmental Health Sciences, School of Public Health, University at Albany, Rensselaer, New York 12144, USA.

Abstract

We investigated the mechanisms whereby omega-3 and -6 polyunsaturated fatty acids (PUFAs) cause cell death of mouse thymocytes using flow cytometry, focusing on the respective roles of intracellular calcium concentration, [Ca(2+)](i) and reactive oxygen species (ROS). We applied the C-22, 20, and 18 carbon omega-3 (DHA, EPA, ALA) and omega-6 (DTA, ARA, and LNA) fatty acids to isolated thymocytes and monitored cell death using the DNA-binding dye, propidium iodide. When applied at 20 µM concentration, omega-3 fatty acids killed thymocytes over a period of 1 h with a potency of DHA > EPA > ALA. The omega-6 PUFAs were more potent. The C18 omega-6 fatty acid, LNA, was the most potent, followed by DHA and ARA. Cell death was always accompanied by an increase in the levels of [Ca(2+)](i) and ROS. Both increases were in proportion to the potency of the PUFAs in inducing cell death. Removing extracellular calcium did not prevent the elevation in [Ca(2+)](i) nor cell death. However, the intracellular calcium chelator, BAPTA, almost totally reduced both the elevation in [Ca(2+)](i) and cell death, while vitamin E reduced the elevation in ROS and cell death. BAPTA also prevented the elevation in ROS, but vitamin E did not prevent the elevation in [Ca(2+)](i). Thapsigargin, which depletes endoplasmic reticulum calcium, blocked the elevation in [Ca(2+)](i), but CCCP, a mitochondrial calcium uptake inhibitor, did not. These results suggest that the six PUFAs we studied kill thymocytes by causing release of calcium from endoplasmic reticulum, which causes release of ROS from mitochondria which leads to cell death.

PMID:
20589836
DOI:
10.1002/jcp.22290
[Indexed for MEDLINE]

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