title: Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice.
abstract: We recently demonstrated that (n-3) PUFA trigger the induction of apoptosis in the colon by enhancing phospholipid oxidation and mitochondrial Ca2+ accumulation. To further elucidate the mechanisms regulating oxidative stress-induced apoptosis in vivo, a 2 x 2 experiment was designed using both wild type (control) and manganese-dependent superoxide dismutase (SOD2) heterozygous knockout mice (SOD2(+/-)), which exhibit increased mitochondrial oxidative stress. Mice were fed diets differing only in the type of fat [corn oil or fish oil containing (n-3) PUFA] at 15% by weight for 4 wk. Dietary (n-3) PUFA treatment enhanced (22%) apoptosis in colonic crypts. In addition, SOD2 haploinsufficiency enhanced (20%) apoptosis, which was further increased (36%) by (n-3) PUFA feeding. Dietary lipid source and genotype interactively modulated nitrotyrosine levels (P = 0.027) and inflammation (P = 0.032). These findings demonstrate that the proapoptotic effects of (n-3) PUFA are enhanced in oxidatively stressed SOD2(+/-) mice. Thus, (n-3) PUFA appear to promote an oxidation-reduction imbalance in the intestine, which may directly or indirectly trigger apoptosis and thereby reduce colon cancer risk.
authors.affiliation: Program in Integrative Nutrition and Complex Diseases, Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Yang-Yi
authors.initials: YY
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhan
authors.forename: Harold M
authors.initials: HM
authors.lastname: Aukema
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Davidson
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Evelyn
authors.initials: E
authors.lastname: Callaway
authors.forename: Yanan
authors.initials: Y
authors.lastname: Tian
authors.forename: Brad R
authors.initials: BR
authors.lastname: Weeks
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Lupton
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Robert S
authors.initials: RS
authors.lastname: Chapkin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D017931:DNA Primers; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006580:Genetic Carrier Screening; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics
chemical_list: D017931:DNA Primers; D015525:Fatty Acids, Omega-3; D013482:Superoxide Dismutase