Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice.
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.
Fan
Yang-Yi
YY
Program in Integrative Nutrition and Complex Diseases, Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843, USA.
Zhan
Yang
Y
Aukema
Harold M
HM
Davidson
Laurie A
LA
Zhou
Lan
L
Callaway
Evelyn
E
Tian
Yanan
Y
Weeks
Brad R
BR
Lupton
Joanne R
JR
Toyokuni
Shinya
S
Chapkin
Robert S
RS
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
D017931:DNA Primers; D015525:Fatty Acids, Omega-3; D013482:Superoxide Dismutase