Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice. Academic Article uri icon


  • 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.

published proceedings

  • J Nutr

author list (cited authors)

  • Fan, Y., Zhan, Y., Aukema, H. M., Davidson, L. A., Zhou, L., Callaway, E., ... Chapkin, R. S.

citation count

  • 20

complete list of authors

  • Fan, Yang-Yi||Zhan, Yang||Aukema, Harold M||Davidson, Laurie A||Zhou, Lan||Callaway, Evelyn||Tian, Yanan||Weeks, Brad R||Lupton, Joanne R||Toyokuni, Shinya||Chapkin, Robert S

publication date

  • January 2009