TY - JOUR
T1 - Neuronal hemoglobin affects dopaminergic cells' response to stress
AU - Codrich, Marta
AU - Bertuzzi, Maria
AU - Russo, Roberta
AU - Francescatto, Margherita
AU - Espinoza, Stefano
AU - Zentilin, Lorena
AU - Giacca, Mauro
AU - Cesselli, Daniela
AU - Beltrami, Antonio Paolo
AU - Ascenzi, Paolo
AU - Zucchelli, Silvia
AU - Persichetti, Francesca
AU - Leanza, Giampiero
AU - Gustincich, Stefano
PY - 2017/1/5
Y1 - 2017/1/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85008936578&partnerID=8YFLogxK
U2 - 10.1038/cddis.2016.458
DO - 10.1038/cddis.2016.458
M3 - Article
SN - 2041-4889
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 1
M1 - e2538
ER -
