Adenosine A(2)A receptor but not HIF-1 mediates Tyrosine hydroxylase induction in hypoxic PC12 cells
Authors: Elena Gammella
Lorenza Tacchini
Gaetano Cairo
Journal: Journal of neuroscience research (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Tyrosine hydroxylase; catecholamines; adenosine; A(2)A receptor; HIF-1
Affiliations: Department of Human Morphology and Biomedical Sciences, Città Studi, Università degli Studi di Milano, Milan, Italy.

Abstract:  Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamines released by oxygen-sensitive cells in response to hypoxic conditions. Adenosine is released in response to hypoxia in the central nervous system and CGS21680, an adenosine A(2)A receptor agonist, induces TH transcription. As we have previously demonstrated the A(2)A receptor-mediated induction of HIF-1 in macrophages and hepatocytes, we investigated the involvement of HIF-1 in the adenosine-mediated activation of TH expression. Exposure to adenosine or CGS21680 increased TH mRNA and protein levels in PC12 cells. Transcription of a reporter gene under the control of the wild type rat TH promoter was induced 3.5-fold in CGS21680-treated cells, but neither the mutation of the hypoxia responsive element in the TH promoter nor the co-transfection of a dominant negative of the HIF-1 beta subunit prevented the increase in transcription; furthermore, CGS21680 increased CREB binding activity but did not induce HIF-1 DNA binding activity or protein levels. To investigate whether HIF-1 was involved in the hypoxia-mediated induction of TH, PC12 cells were exposed to hypoxia in the presence of the A(2)A receptor antagonist ZM241385, which prevented hypoxia-dependent TH induction despite HIF-1 activation; in line with this finding, the inhibition of HIF-1 did not abolish TH induction in hypoxic PC12 cells. These results indicate that, under hypoxic conditions, TH (a key factor in systemic adaptation to reduced oxygen availability) is not regulated by HIF-1, the primary modulator of the response to hypoxia, but by the adenosine A(2)A receptor-mediated signalling pathway. 

Retracted: No

PubPeer comments:
 Approximately half of the Springer copyrighted paper:  [**Objective Image Quality Evaluation for JPEG, JPEG 2000, and Vidware Vision**]  Chung-Hao Chen, Yi Yao, David L. Page, Besma Abidi, Andreas Koschan, Mongi Abidi [University of Tennessee] was republished in the Research Science Press copyrighted version:  [**Comparison of Image Compression Methods Using Objective Measures towards Machine Recognition**]  IJIAP International Journal of Information Analysis and Processing, [Vol. I, No.2, October 2008] The later version did not enclose copied passages in quotation marks, did not cite the source, and did not indicate permission from copyright-holder Springer. The manuscript was submitted April 30, 2008, after the 2006 Springer version had already been published. The following week, on May 6, 2008, the manuscript was additionally submitted to, and then published by, CSES. The CSES copyrighted version bore the identical title of the Research Science Press copyrighted version:  [**Comparison of Image Compression Methods Using Objective Measures towards Machine Recognition**] The CSES version did not enclose copied passages in quotation marks, did not cite either source, and did not indicate permission from copyright-holder Springer or copyright-holder Research Science Press. It copied the entirety of the Research Science Press version. The work was funded by the US Department of Energy under grant DOE-DE-FG52- 2004NA25589 and by the the US Department of Defense DOD RDECOM NAC ARC Program under grant W56HZV-04-2-0001. Examples are shown below, with the Springer version on the left, highlightted green, and the two later (identical) versions highlighter blue. Figures from the Springer version were reversed horizontally in the later versions. ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ,