Butterfat fatty acids differentially regulate growth and differentiation in Jurkat T-cells.
Synthetic Conjugated Linoleic Acid mixture (CLA; c9,t11; t10,c12-18:2) has been previously shown to inhibit growth, and enhance apoptosis and IL-2 mRNA synthesis in human lymphoblastic Jurkat T-cells. In this study, two different butterfat types were evaluated and compared for their effects on Jurkat cell viability, oxidative stress, pro-apoptotic activity, and cytokine synthesis: the conventionally produced butterfat (CBF), and organic butterfat (OBF) containing significantly higher amounts of c9,t11 (Rumenic Acid, RA), trans-vaccenic acid (VA; t11-18:1), alpha-linolenic acid (ALA), and lower levels of linoleic acid (LA). Results from cell treatment with both butterfat mixtures showed comparable oxidative stress (superoxide production, intracellular GSH depletion,and lipid peroxides yield), NADPH oxidase activation, cytotoxicity (LDH release), and IL-2 transcript level, whereas the effects of enhanced growth-inhibitory and pro-apoptotic activities were associated with OBF treatment. To then investigate each butterfat-induced effect caused by RA, VA, LA, and ALA, cells were exposed to synthetic FA concentrations similar to those from the different butterfats. Higher oxidative stress (superoxide production, intracellular GSH depletion) was induced by alpha-linolenic (ALA) and linoleic (LA) incubation (P<0.01) and superoxide production was suppressed by specific PKCalpha inhibitor (Gö 6976) and linked to increased toxicity and IL-2 synthesis inhibition. By contrast, cell treatment with RA increased apoptosis and IL-2 synthesis. These results suggest that a supply of ALA and LA is responsible for BF-induced oxidative stress via PKCalpha-NADPH oxidase pathway, and that enhanced antiproliferative effects in OBF treated cells is essentially determined by RA-induced pro-apoptotic activity.
Bergamo
Paolo
P
Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy. p.bergamo@isa.cnr.it
Luongo
Diomira
D
Maurano
Francesco
F
Rossi
Mauro
M
D000838:Anions / Q000737:chemistry; D002079:Butter / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D000838:Anions; D005227:Fatty Acids; D007376:Interleukin-2; D017962:alpha-Linolenic Acid; D013481:Superoxides; D002079:Butter; D019255:NADPH Oxidases; D011493:Protein Kinase C