Neuronal hemoglobin affects dopaminergic cells' response to stress.

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

SUBMITTER: Codrich M 

PROVIDER: S-EPMC5386368 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature