Differential effects of hypoxia on untreated and NGF treated PC12 cells

Citation
J. Gross et al., Differential effects of hypoxia on untreated and NGF treated PC12 cells, LIFE SCI, 67(21), 2000, pp. 2595-2603
Citations number
27
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
00243205 → ACNP
Volume
67
Issue
21
Year of publication
2000
Pages
2595 - 2603
Database
ISI
SICI code
0024-3205(20001013)67:21<2595:DEOHOU>2.0.ZU;2-#
Abstract
Perinatal hypoxia is known to induce long-lasting changes in the central do paminergic system. In order to understand the cellular mechanism of these c hanges, we studied the effects of hypoxia on the levels of dopamine (DA) an d tyrosine hydroxylase (TH) mRNA in untreated and NGF treated PC12 cells. O n the second day after plating (DAP), cells were exposed to a hypoxic episo de (pO(2) = 10-20 mm Hg, 24 h), and the levels of DA and TH mRNA were exami ned on DAP 4 and DAP 8. In untreated cells, hypoxia induced a two fold incr ease both in DA and TH mRNA levels on DAP 4 which normalized up to DAP 8. T his increase correlated with an activation of the hypoxia inducible factor (HIF-1alpha), measured with a reporter gene. In contrast, NGF treated cells responded to hypoxia with an increase of DA level on DAP 8. In these cells neither an increase of the HIF-1 alpha activity measured immediately after hypoxia nor a significant increase of the TH mRNA level on DAP 8 were foun d. The findings indicate that NGF shifts the hypoxia induced changes of DA levels from a short-term to a long-term mode. The long-term increase of dop amine levels is the most likely result of changes connected with cell growt h and differentiation and not the result of a long-term TH mRNA level incre ase. (C) 2000 Elsevier Science Inc. All rights reserved.