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Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors
Author(s) -
Parga J.A.,
RodríguezPallares J.,
Joglar B.,
DiazRuiz C.,
Guerra M.J.,
LabandeiraGarcia J.L.
Publication year - 2010
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22474
Subject(s) - dopaminergic , nadph oxidase , biology , apocynin , glibenclamide , potassium channel , microbiology and biotechnology , tyrosine hydroxylase , mitochondrion , reactive oxygen species , dopamine , endocrinology , diabetes mellitus
Abstract Reactive oxygen species signaling has been suggested to regulate stem cell development. In the present study, we treated neurospheres of rat mesencephalic precursors with inhibitors of the NADPH oxidase complex and mitochondrial ATP‐sensitive potassium (mitoKATP) channel blockers during the proliferation and/or the differentiation periods to study the effects on generation of dopaminergic neurons. Treatment with low doses (100 or 250 μM) of the NADPH inhibitor apocynin during the proliferation period increased the generation of dopaminergic neurons. However, higher doses (1 mM) were necessary during the differentiation period to induce the same effect. Treatment with general (glibenclamide) or mitochondrial (5‐hydroxydecanoate) KATP channel blockers during the proliferation and differentiation periods increased the number of dopaminergic neurons. Furthermore, neither increased proliferation rate nor apoptosis had a major role in the observed increase in generation of dopaminergic neurons, which suggests that the redox state is able to regulate differentiation of precursors into dopaminergic neurons. Developmental Dynamics 239:3247–3259, 2010. © 2010 Wiley‐Liss, Inc.