Otton Rosemari, Curi Rui
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, 05508-900 Butantan, São Paulo, SP, Brazil.
Toxicol In Vitro. 2005 Sep;19(6):749-55. doi: 10.1016/j.tiv.2005.04.003.
The effect of a mixture of fatty acids upon lymphocyte and leukaemia cell death was examined. Peripheral lymphocytes from healthy subjects and two human leukaemia cell lines-Jurkat (T lymphocyte) and Raji (B lymphocyte) cells-were treated with increasing concentrations (0.1-0.4 mM) of a fatty acid mixture in a proportion mimicking that of the free fatty acids in plasma. Features of cell death were then evaluated. Phosphatidylserine externalization, and DNA fragmentation (apoptosis), and loss of cell membrane integrity (necrosis) and mitochondrial depolarization (common feature of cell death) were observed in leukaemia cells after the fatty acid treatment for up to 48 h. Human lymphocytes, however, when submitted to the same treatment presented apoptotic feature only. These findings indicate that a free fatty acid mixture (mimicking the proportion found in plasma) triggers apoptosis of leukaemia cell lines followed by loss of cell membrane integrity, whereas in human circulating lymphocytes the same treatment causes apoptosis only. Evidence is presented herein that mitochondria from leukaemic cells are more susceptible to the toxicity of the fatty acids than mitochondria from human circulating lymphocytes.
研究了脂肪酸混合物对淋巴细胞和白血病细胞死亡的影响。用浓度递增（0.1 - 0.4 mM）的脂肪酸混合物处理健康受试者的外周淋巴细胞以及两种人类白血病细胞系——Jurkat（T淋巴细胞）和Raji（B淋巴细胞）细胞，脂肪酸混合物的比例模拟血浆中游离脂肪酸的比例。然后评估细胞死亡的特征。在脂肪酸处理长达48小时后，在白血病细胞中观察到磷脂酰丝氨酸外翻、DNA片段化（凋亡）、细胞膜完整性丧失（坏死）以及线粒体去极化（细胞死亡的常见特征）。然而，人类淋巴细胞在接受相同处理时仅呈现凋亡特征。这些发现表明，游离脂肪酸混合物（模拟血浆中发现的比例）引发白血病细胞系凋亡，随后导致细胞膜完整性丧失，而在人类循环淋巴细胞中，相同处理仅导致凋亡。本文提供的证据表明，白血病细胞的线粒体比人类循环淋巴细胞的线粒体对脂肪酸的毒性更敏感。
