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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 Engrailed 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. RNA-seq data for differentially expressed genes in the SNpc of En1+/- mice, En2 infused mice and 6-OHDA/En2 injection experiments.

ORGANISM(S): Mus musculus

SUBMITTER: Hocine Rekaik

PROVIDER: E-GEOD-72321 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Engrailed homeoprotein protects mesencephalic dopaminergic neurons from oxidative stress

Project description: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 Engrailed 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.

2015-09-24 | GSE72321 | GEO

Mus musculus

Project description:Engrailed homeoprotein protects mesencephalic dopaminergic neurons from oxidative stress

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Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T cell blast crisis

Project description:Deregulations in transcription factors lead to abnormal development, like in leukaemias, where chromosomal abnormalities either create chimeric TFs or alter the expression of the existing ones. The characterization of the precise functions of the TFs that regulate blood formation is essential to understand how these mechanisms are altered in malignancies. We have found that Engrailed-2 becomes methylated in the progression to blast crises of T-cell phenotype in chronic myelogenous leukaemia (CML) in human samples. Subsequently we found that En2 is expressed during T-cell development in the mouse and in humans. Engrailed-2 plays an essential role in central nervous system development but it has not been shown to participate in haematopoiesis. Many TFs have been found to play essential functions both in nervous system and blood development, thus making En2 a likely candidate to be involved in haematopoiesis. We have studied haematopoiesis of wild-type vs. En2 knockout mice. To increase our understanding of the possible molecular role(s) of En2 during T cell development, we have compared by microarray analysis the gene expression patterns of En2-/- versus WT sorted DP thymocytes and also CD8+ splenocytes (the two populations in which we had detected En2 expression).

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Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T cell blast crisis

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Nigral Transcriptomic Profiles in Engrailed-1 Hemizygous Mouse Models of Parkinson’s Disease Reveal Upregulation of Oxidative Phosphorylation-Related Genes Associated with Resistance to Dopaminergic Neurodegeneration

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