title: Engrailed Homeoprotein Protects Mesencephalic Dopaminergic Neurons from Oxidative Stress.
abstract: Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress, and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed1 heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks, and protects dopaminergic neurons against apoptosis.
authors.affiliation: Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Hocine
authors.initials: H
authors.lastname: Rekaik
authors.affiliation: Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Blaudin de Thé
authors.affiliation: Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Fuchs
authors.affiliation: Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Massiani-Beaudoin
authors.affiliation: Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France. Electronic address: alain.prochiantz@college-de-france.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
authors.affiliation: Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Rajiv L
authors.initials: RL
authors.lastname: Joshi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006570:Heterochromatin / Q000235:genetics; D018398:Homeodomain Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D000099266:Engrailed 2 Protein
chemical_list: D006570:Heterochromatin; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D000099266:Engrailed 2 Protein; C080330:En1 protein, mouse