Induction of apoptosis and apoptotic mediators in Balb/C splenic lymphocytes by dietary n-3 and n-6 fatty acids.
The present study was designed to investigate the effect of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on anti-CD3 and anti-Fas antibody-induced apoptosis and its mediators in mouse spleen cells. Nutritionally adequate semipurified diets containing either 5% w/w corn oil (n-6 PUFA) or fish oil (n-3 PUFA) were fed to weanling female Balb/C mice, and 24 wk later mice were sacrificed. In n-3 PUFA-fed mice, serum and splenocyte lipid peroxides were increased by 20 and 28.3% respectively, compared to n-6 PUFA-fed mice. Further, serum vitamin E levels were decreased by 50% in the n-3 PUFA-fed group, whereas higher anti-Fas- and anti-CD3-induced apoptosis (65 and 66%) and necrosis (17 and 25%), compared to the n-6 PUFA-fed group, were found when measured with Annexin V and propidium iodide staining, respectively. In addition, decreased Bcl-2 and increased Fas-ligand (Fas-L) also were observed in the n-3 PUFA-fed group compared to the n-6 PUFA-fed group. No difference in the ratio of splenocyte subsets nor their Fas expression was observed between the n-3 PUFA-fed and n-6 PUFA-fed groups, whereas decreased proliferation of splenocytes was found in n-3 PUFA-fed mice compared to n-6 PUFA-fed mice. In conclusion, our results indicate that dietary n-3 PUFA induces higher apoptosis by increasing the generation of lipid peroxides and elevating Fas-L expression along with decreasing Bcl-2 expression. A reduced proliferative response of immune cells also was observed in n-3 PUFA-fed mice.
Avula
C P
CP
Department of Medicine, The University of Texas Health Science Center at San Antonio, 78289-7879, USA.
Zaman
A K
AK
Lawrence
R
R
Fernandes
G
G
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D003314:Corn Oil; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D053222:Fas Ligand Protein; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils; D008054:Lipid Peroxides / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013154:Spleen / Q000166:cytology*; D014886:Weaning; D019014:fas Receptor / Q000032:analysis
D004042:Dietary Fats, Unsaturated; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D008054:Lipid Peroxides; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D003314:Corn Oil