title: Prevention of age-related changes in rat cortex transcription factor activator protein-1 by hypolipidemic drugs.
abstract: We sought to investigate if, similar to what has been described in other rodent tissues, ageing changes the activity of several transcription factors, namely signal transducer and activator of transcription, nuclear factor-kappa B (NFkappaB), activated protein-1 (AP-1) and peroxisome proliferator-activated receptor (PPAR), in cortex of Sprague-Dawley rats. We also investigated if the administration of two hypolipidemic drugs, gemfibrozil (GFB) and atorvastatin (ATV), could prevent those changes. To this purpose, we determined the expression and binding activity of these transcription factors in cortex samples from 3-month and 18-month old male and female rats, and in 18-month old rats of both sexes treated for 21 days with a daily dose of 3mg GFB/kg or 10mg ATV/kg. Ageing increased rat cortex NFkappaB binding activity by 35-40%, and decreased by 22-26% the amount of PPARalpha in rats of both sexes, while cortex AP-1 binding activity and c-Jun content were reduced only in old females (-26 and -50%, respectively). Cortex cyclooxigenase-2 (COX-2) and receptor for activated C-kinase 1 (RACK1) expression was also reduced by old age. Hypolipidemic drugs prevented the age-related decrease of cortex AP-1 in old females and increased AP-1 binding activity and c-Jun protein in cortex from both old male and female rats. GFB increased also by 80% the cortex PPARalpha content in old males. Our data indicate that 18-month old rats show signs of cortex biochemical deterioration related to the ageing process, and that hypolipidemic drug administration partially prevents the appearance of some of the age-related changes in cortex biochemistry.
authors.affiliation: Unidad de Farmacología y Farmacognosia, Facultad de Farmacia, Universidad de Barcelona Avda Diagonal 643, 08028 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sanguino
authors.forename: Núria
authors.initials: N
authors.lastname: Roglans
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
authors.forename: Juan C
authors.initials: JC
authors.lastname: Laguna
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D007527:Isoenzymes; D016328:NF-kappa B; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015248:Gemfibrozil