title: Grape antioxidant dietary fibre prevents mitochondrial apoptotic pathways by enhancing Bcl-2 and Bcl-xL expression and minimising oxidative stress in rat distal colonic mucosa.
abstract: Grape antioxidant dietary fibre (GADF) is a grape product rich in dietary fibre and natural antioxidants. We reported previously that GADF intake reduced apoptosis and induced a pro-reducing shift in the glutathione (GSH) redox status of the rat proximal colonic mucosa. The aim of the study was to elucidate the molecular mechanisms responsible for the anti-apoptotic effect of GADF and their association with the oxidative environment of the distal colonic mucosa. The ability of GADF to modify colonic crypt cell proliferation was also investigated. Male Wistar rats (n 20) were fed with diets containing either cellulose (control group) or GADF (GADF group) as fibre for 4 weeks. GADF did not modify cell proliferation but induced a significant reduction of colonic apoptosis. The anti-apoptotic proteins Bcl-2 (B-cell lymphoma-2) and Bcl-xL (B-cell lymphoma extra large) were up-regulated in the mitochondria and down-regulated in the cytosol of the GADF mucosa, whereas the opposite was found for the pro-apoptotic protein Bax (Bcl-2-associated X protein), leading to an anti-apoptotic shift in the pattern of expression of the Bcl-2 family. Cytosolic cytochrome c and cleaved caspase-3 levels and caspase-3 activity were reduced by GADF. The modulation of the antioxidant enzyme system and the increase of the cytosolic GSH:glutathione disulfide (GSSG) ratio elicited by GADF helped to reduce oxidative damage. The cytosolic GSH:GSSG ratio was negatively related to apoptosis. These results indicate that GADF acts on the expression of the pro- and anti- apoptotic Bcl-2 proteins, attenuating the mitochondrial apoptotic pathway in the distal colonic mucosa. This effect appears to be associated with the antioxidant properties of GADF.
authors.affiliation: Sección Departamental de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. elopez@farm.ucm.es
authors.forename: María Elvira
authors.initials: ME
authors.lastname: López-Oliva
authors.forename: María José
authors.initials: MJ
authors.lastname: Pozuelo
authors.forename: Rafael
authors.initials: R
authors.lastname: Rotger
authors.forename: Emilia
authors.initials: E
authors.lastname: Muñoz-Martínez
authors.forename: Isabel
authors.initials: I
authors.lastname: Goñi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D003106:Colon / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004043:Dietary Fiber / Q000378:metabolism*; D015536:Down-Regulation; D005638:Fruit / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D027843:Vitis / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D004043:Dietary Fiber; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D005978:Glutathione