title: Rat embryo exposure to all-trans retinoic acid results in postnatal oxidative damage of respiratory complex I in the cerebellum.
abstract: The results of the present work show that the exposure of pregnant rats to low doses of all-trans-retinoic acid (ATRA) (2.5 mg/kg body weight) results in postnatal dysfunction of complex I of the respiratory chain in the cerebellum of the offspring. ATRA had no effect on the postnatal expression of complex I and did not exert any direct inhibitory effect on the enzymatic activity of the complex. The ATRA embryonic exposure resulted, however, in a marked increase in the level of carbonylated proteins in the mitochondrial fraction of the cerebellum, in particular of complex I subunits. The postnatal increase of the carbonylated proteins correlated directly with the inhibition of the activity of complex I. ATRA had, on the other hand, no effect on oxygen free-radical scavengers. It is proposed that embryonic exposure to ATRA results in impairment of protein surveillance in the cerebellum, which persists after birth and results in accumulation of oxidatively damaged complex I.
authors.affiliation: Department of Medical Biochemistry, Biology and Physics, University of Bari Aldo Moro, Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Signorile
authors.forename: Nicola
authors.initials: N
authors.lastname: Sardaro
authors.forename: Domenico
authors.initials: D
authors.lastname: De Rasmo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.forename: Pietro
authors.initials: P
authors.lastname: Borracci
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Carratù
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000201:enzymology*; D011897:Random Allocation; D051381:Rats; D014212:Tretinoin / Q000633:toxicity*
chemical_list: D014212:Tretinoin; D042967:Electron Transport Complex I