title: α-Tocopherol administration blocks adaptive changes in cell NADH/NAD+ redox state and mitochondrial function leading to inhibition of gastric mucosa cell proliferation in rats.
abstract: In experimentally induced chronic gastritis, a compensatory mucosal cell proliferation occurs with enhanced glucose oxidative metabolism linked to lipoperoxidative events. Therefore, this study was aimed at assessing the participation of cell NAD/NADH redox state and mitochondrial functions during gastric mucosa proliferation and the effects of in vivo α-tocopherol (vitamin E) administration. Glucose oxidation and oxygen consumption were tested in gastric mucosa samples obtained from rats with gastritis and from those also treated with α-tocopherol. Gastric mucosal mitochondria were isolated and structural and functional parameters were determined. Succinate oxidation, ADP phosphorylation, mitochondrial enzyme activities, and membrane lipid composition were measured. In addition, parameters indicative of cellular NAD/NADH redox state, proliferation, apoptosis, and nitric oxide (NO) metabolism were also determined. After ethanol withdrawal, the damaged gastric mucosa increased glucose and oxygen consumption, events associated with a more reduced cytoplasmic NAD/NADH ratio. Enhanced mitochondrial oxidative phosphorylation and increased mitochondrial enzyme activities occurred early, accompanied by recovery of lost mitochondrial protein and lipid composition in the gastric mucosa, events associated with increased NO production. When mitochondrial function and structural events were normalized, apoptosis was initiated as assessed by the mitochondrial Bax/Bcl2 ratio. Treatment with α-tocopherol inhibited cell proliferation and blocked enhanced glucose utilization, mitochondrial substrate oxidation, and changes in redox state, delaying the onset of these adaptive metabolic changes, whereas it inhibited cell proliferation. In conclusion, α-tocopherol could abolish damage-induced "stress" signaling by desynchronizing mitochondrial adaptive responses, including mitochondria biogenesis, and consequently NAD/NADH redox, which seems to regulate gastric mucosal cell proliferation.
authors.affiliation: Instituto de Fisiología Celular, Departamento de Biología Celular y Desarrollo, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510, DF, Mexico.
authors.forename: Marisela
authors.initials: M
authors.lastname: Olguín-Martínez
authors.affiliation: Instituto de Fisiología Celular, Departamento de Biología Celular y Desarrollo, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510, DF, Mexico.
authors.forename: Diego R
authors.initials: DR
authors.lastname: Hernández-Espinosa
authors.affiliation: Instituto de Fisiología Celular, Departamento de Biología Celular y Desarrollo, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510, DF, Mexico. Electronic address: rhernand@ifc.unam.mx.
authors.forename: Rolando
authors.initials: R
authors.lastname: Hernández-Muñoz
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects*; D002956:Citrulline / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005756:Gastritis / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010101:Oxygen Consumption; D017208:Rats, Wistar; D024502:alpha-Tocopherol / Q000008:administration & dosage*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D009573:Nitrites; D051028:bcl-2-Associated X Protein; D009243:NAD; D002956:Citrulline; D024502:alpha-Tocopherol; D005947:Glucose
keywords: Bax/Bcl2 ratio; CD; Cox; Experimental gastritis; Free radicals; Glucose oxidation; IDH; LP; MDH; Mitochondrial function; Nitric oxide; RCR; ROS; SDH; TCA; conjugated diene; cytochrome c oxidase; isocitrate dehydrogenase; lipid peroxidation; malate dehydrogenase; reactive oxygen species; respiratory control ratio; succinate dehydrogenase; tricarboxylic acid