Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus. Neurochemical stress induces epigenetic modifications, nucleolar alterations and autophagy inhibition that depend on Hb expression. When adeno-associated viruses carrying α- and β-chains of Hb are stereotaxically injected into mouse SN, Hb forms aggregates and causes motor learning impairment. These results position Hb as a potential player in DA cells' homeostasis and dysfunction in PD. Copyright The Author(s) 2017

Neuronal hemoglobin affects dopaminergic cells' response to stress / Codrich, Marta; Bertuzzi, Maria; Russo, Roberta; Francescatto, Margherita; Espinoza, Stefano; Zentilin, Lorena; Giacca, Mauro; Cesselli, Daniela; Beltrami, Antonio Paolo; Ascenzi, Paolo; Zucchelli, Silvia; Persichetti, Francesca; Leanza, Giampiero; Gustincich, Stefano. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 8:1(2017), pp. 1-12. [10.1038/cddis.2016.458]

Neuronal hemoglobin affects dopaminergic cells' response to stress

Codrich, Marta;Bertuzzi, Maria;Russo, Roberta;Giacca, Mauro;Zucchelli, Silvia;Gustincich, Stefano
2017-01-01

Abstract

Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus. Neurochemical stress induces epigenetic modifications, nucleolar alterations and autophagy inhibition that depend on Hb expression. When adeno-associated viruses carrying α- and β-chains of Hb are stereotaxically injected into mouse SN, Hb forms aggregates and causes motor learning impairment. These results position Hb as a potential player in DA cells' homeostasis and dysfunction in PD. Copyright The Author(s) 2017
2017
8
1
1
12
e2538
10.1038/cddis.2016.458
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386368/
Codrich, Marta; Bertuzzi, Maria; Russo, Roberta; Francescatto, Margherita; Espinoza, Stefano; Zentilin, Lorena; Giacca, Mauro; Cesselli, Daniela; Beltrami, Antonio Paolo; Ascenzi, Paolo; Zucchelli, Silvia; Persichetti, Francesca; Leanza, Giampiero; Gustincich, Stefano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/48752
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