Mechanisms involved in Jurkat cell death induced by oleic and linoleic acids.
OBJECTIVE
Previous study from our laboratory showed the toxicity of oleic (OA) and linoleic acids (LA) on Jurkat and Raji cells and human lymphocytes in vitro. The mechanisms involved in the toxicity induced by OA and LA on Jurkat cells were determined in vitro.


METHODS
Jurkat cells were treated in the presence of OA and LA (25, 50, 100 and 200muM). The parameters investigated were: triglycerides and cholesterol ester concentrations determined by enzymatic assay, activation of peroxisome proliferator activated receptor (PPAR) by electrophoretic mobility shift assay, caspase 3, 6 and 8 activities by spectrofluorometric assay, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma production by enzyme linked absorbent assay (ELISA), expression of pro- (Bax) and anti- (Bcl-2) apoptotic genes by real time polymerase chain reaction and expression of pleiotropic genes by macroarray technique


RESULTS
Evidence is presented herein that the increase in triglycerides concentrations induced by OA is more pronounced than that caused by LA in Jurkat cells. Importantly, triglycerides accumulation may be a mechanism to protect lymphocytes against the toxicity induced by fatty acids. Both fatty acids raised PPAR activation, caspase 3 and 6 activities and TNF-alpha production. LA in toxic concentrations modulated the expression of genes related to cell cycle, apoptosis, proliferation, oxidative stress, and cytokine receptors.


CONCLUSIONS
The findings reported herein support the cell death induced by OA and LA involved triglycerides accumulation, PPAR activation, caspase 3 and 6 activities and TNF-alpha production.
Fernanda Cury-Boaventura
Maria
M
Department of Physiology and Biophysics, Institute of Biomedical Sciences, Av. Prof. Lineu Prestes, 1524, CEP 05508-900, University of São Paulo, SP, Brazil. mafecury@icb.usp.br
Cristine Kanunfre
Carla
C
Gorjão
Renata
R
Martins de Lima
Thaís
T
Curi
Rui
R
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D019169:Jurkat Cells / Q000187:drug effects*; D019787:Linoleic Acid / Q000494:pharmacology* / Q000633:toxicity; D019301:Oleic Acid / Q000494:pharmacology* / Q000633:toxicity; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014280:Triglycerides / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid; D007371:Interferon-gamma; D019787:Linoleic Acid; D020169:Caspases