Oxygen tension modulates neurite outgrowth in PC12 cells through a mechanism involving HIF and VEGF.

Journal of Molecular Neuroscience : MN
Damian C GenetosJ Kent Leach

Abstract

Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1alpha stabilization. The hypoxic target gene Vegf was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment v...Continue Reading

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Citations

Jan 8, 2013·Neurochemical Research·Lihua KangZhengming Zhou
Dec 15, 2015·Neuroscience Letters·Longbo ZhangAngélique Bordey
Sep 29, 2011·Neuroscience Letters·Young-Soon KangSoo-Kyung Bae
Jan 25, 2011·Translational Research : the Journal of Laboratory and Clinical Medicine·Meghan G ThomasLivia Hool
Oct 18, 2011·Journal of Neuroscience Research·Jing ZhuGabriele V Ronnett
Oct 8, 2014·Molecular Neurobiology·Wen-Chin WengHsinyu Lee
Apr 22, 2015·ACS Medicinal Chemistry Letters·Md Imam UddinAshwath Jayagopal
Jul 22, 2014·Advanced Healthcare Materials·Amanda J SutherlandMichael S Detamore
Sep 26, 2013·The Journal of Biological Chemistry·Donald A McCarthyJ Andres Melendez

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