Faculty Articles

Title

Alterations in Doublecortin Expression in Human Neuronal Stem Cells in Response to Angiotensinergic Stimulation in Proliferation and Differentiation Conditions

Document Type

Article

Publication Date

4-1-2016

Publication Title

The FASB Journal

Abstract

Activation or inhibition of the renin-angiotensin system (RAS) affects neuronal function and viability. We showed previously that AT2 selective stimulation of human neuronal stem cells (H-9 derived, Life Technologies) increased cell numbers in both differentiation and proliferation medium compared to control and AT1 stimulated human neuronal stem cells. We now show that doublecortin expression in human neuronal stem cells which were seeded in chamber slides and cultured under proliferation (with EGF and FGF-2) or differentiation (no added growth factors) conditions is altered with chronic exposure to AT1 and AT2 selective agonists. Conditions included 14 days treatment with once daily addition of the AT2 selective agonist CGP42112 (final concentration 100 nM); once daily treatment with the non-selective Ang II receptor agonist Sar1 angiotensin II (100 nM) plus the AT2 receptor selective antagonist PD123319 (10 μM) for selective AT1 receptor stimulation; once daily treatment with PD123319 (10 μM) alone; or once daily treatment with vehicle. Following treatment, cells were immunostained for the neuroblast marker doublecortin. Doublecortin expression was reduced by AT1 selective stimulation in differentiation conditions relative to control (Control 70.9 ± 17% and AT1 14.0 ± 6.2%, p<0.01), AT2 stimulated (AT2 86.7 ± 0.6%, p<0.01) and AT2 antagonized with PD123319 (PD123319 64.4 ± 9.3%, p<0.05). In proliferation conditions, doublecortin expression was reduced by AT2 selective stimulation and AT2 antagonism compared to control and AT1 selectively stimulated cells (p<0.01: Control 96.5 ± 1.1% ; AT1 88.7 ± 1.6% ; AT2 9.1 ± 6.1% ; PD123319 2.6 ± 1.0%). These results suggest that angiotensinergic inhibition of doublecortin expression is dependent upon the presence of the growth factors EGF and FGF-2.

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