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. Gunderson, Fragmentation was verified using the Bioanalyzer 2100, and cDNA was hybridized to a GeneChipâ Mouse Gene 2.0 ST array (Affymetrix) at 45 C for 17 h. Following overnight hybridization, chips were washed on the fluidic station FS450 following specific protocols (Affymetrix) and scanned using the GCS 3000 7G scanner. The images were then analyzed with the Expression Console software (Affymetrix) to obtain raw data (CEL files) and metrics for Quality Controls. The observations of some of these metrics and the study of the distribution of raw data showed no outlier sample. CEL files were then normalized and processed to signal intensities using the RMA algorithm from the Bioconductor library and the cdf file V19 from BrainArray. All data for subsequent analysis were then log transformed (base 2) in Partek Genomics Suite. Unsupervised analysis and Anova were used to detect eventual outlier samples and to identify differentially expressed genes. GO PANTHER classification system, Ucp2 +/+ and Ucp2 À/À mice were fed with a diet containing 0.7% (w/w) antioxidant butylated hydroxyanisole (BHA) for 3 weeks prior and all along the AOM/DSS protocol described above. Previously, it has been shown that BHA treatment can enhance glutathione (GSH) levels (Sciuto and Moran, 1999.

. Pecqueur, e3 Western blotting For whole cell extracts, colon tumors were disrupted in lysis buffer (50 mM HEPES pH 7.4, 1.5 mM EDTA, 150 mM NaCl, 10% (v/v) glycerol and 1% (v/v) NP40) supplemented with protease and phosphatase inhibitor cocktails, Cell Reports, vol.28, pp.4-20, 2001.

H. Biorad, C. A. , and U. Ahmed, Primary antibodies to ACC, ACLY, Caspase 3, cleaved Caspase 3, GLUT1, FAS, HK2, LDHA, PKM2 and p-PKM2 were obtained from Cell Signaling, Horseradish peroxidase (HRP)-conjugated anti-rabbit and anti-mouse secondary antibodies were obtained from Jackson ImmunoResearch Laboratories, 2010.

, Roth) overnight at 4 C and then transferred to 70% (v/v) ethanol. The tissues were embedded in paraffin, sectioned at 4 mm thickness and placed on slides. Slides were deparaffinized through three changes of xylene each for 3 min, then rehydrated through descending grades of ethanol to water. Endogenous peroxidases were blocked with 3% (v/v) hydrogen peroxide for 10 min. Antigen retrieval was performed by heating the sections in sodium citrate buffer (10 mM sodium citrate, 0.05% (v/v) Tween-20, pH 6.0) in a rice steamer at 95 C for 10 min, Immunohistochemical staining Colon sections from Ucp2 +/+ and Ucp2 À/À AOM/DSS-treated mice were fixed in Roti-Histofixâ 4% solution

, ) for 90 min at room temperature, followed by incubation with Vectastain ABC system (Vector Laboratories) for 30 min. The detection was made using the DAB substrate kit and slides were counterstained with hematoxylin (Vector Laboratories), The primary antibodies used were our homemade anti-UCP2-605 as well as the anti-UCP2 (ab203244) and anti-Ki67 (ab15580) from Abcam

, Germany) as detailed above. The same procedure as indicated for immunohistochemical staining was followed (except for the inactivation of endogenous peroxidases using hydrogen peroxide). The following primary antibodies were used: homemade anti-UCP2-605 and anti-UCP2 from, Immunofluorescence Colon tissues were fixed in Roti-Histofixâ 4% solution

, The fluorescent secondary antibodies were Alexa Fluor 488 goat anti-rabbit and Alexa Fluor 488 donkey anti-goat (1:400; Invitrogen). Fluorescent image acquisition was performed using the Zeiss AxioObserver Z1 inverted fluorescence microscope coupled with the Zeiss Axiocam MRm

, USA) according to manufacturer recommendations. Protein extracts were obtained as described above, and samples were protected from further oxidation by adding 50 mM DTT. Briefly, 20 mg of tissue lysate were treated with 2,4-dinitrophenylhydrazine (DNPH) to derivatize the carbonyl groups on proteins to 2,4-dinitrophenylhydrazone-tagged products, Protein oxidation assay Samples were stored frozen at À80 C until processing, pp.4-20

, After centrifugation at 1,000 g for 20 min at 4 C, specific enzyme activities were determined on supernatants by spectrophotometric monitoring of product production or substrate disappearance at different UV/ visible light wavelengths. LDH specific activity was measured by adding diluted sample to a cuvette containing 0.25 mM NADH in 100 mM KH 2 PO 4 /K 2 HPO 4 , pH 7.4, at 25 C. Reaction was initiated by the addition of pyruvate at a final concentration of 0.9 mM. LDH activity was monitored by measuring absorbance at 340 nm. G6PDH specific activity was measured by adding samples to a cuvette containing 0.65 mM NADP + in 50 mM Tris-HCl, ph 7.6 at 37 C. Reaction was initiated by the addition of glucose-6-phosphate at a final concentration of 2.5 mM. G6PDH activity was monitored by measuring absorbance at 340 nm. Respiratory chain complex activities were measured as previously described, BioRad) and then transferred to nitrocellulose membranes. After blockade with TBS, 1% (w/v) BSA, 0.1% (v/v) Tween-20 solution, membranes were incubated with antibodies against dinitrophenylhydrazone-modified carbonyl groups, followed by HRP-conjugated secondary antibodies, 2009.

, Cell Reports, vol.28, pp.2306-2316, 2019.