| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Biochemistry and 2Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106
Submitted 24 February 2003 ; accepted in final form 4 April 2003
Regulation of tyrosine hydroxylase (TH) by intermittent hypoxia (IH) was
investigated in rat pheochromocytoma 12 (PC-12) cells by exposing them to
alternating cycles of hypoxia (1% O2, 15 s) and normoxia (21%
O2, 3 min) for up to 60 cycles; controls were exposed to normoxia
for a similar duration. IH exposure increased dopamine content and TH activity
by 
42 and 56%, respectively. Immunoblot analysis revealed that
comparable levels of TH protein were expressed in normoxic and IH cells.
Removal of TH-bound catecholamines and in vitro phosphorylation of TH in
cell-free extracts by the catalytic subunit of protein kinase A (PKA)
increased TH activity in normoxic but not in IH cells, suggesting possible
induction of TH phosphorylation and removal of endogenous inhibition of TH by
IH. To assess the role of serine phosphorylation in IH-induced TH activation,
TH immunoprecipitates and extracts derived from normoxic and IH cells were
probed with anti-phosphoserine and anti-phospho-TH (Ser-40) antibody,
respectively. Compared with normoxic cells, total serine and Ser-40-specific
phosphorylation of TH were increased in IH cells. IH-induced activation of TH
and the increase in total serine and Ser-40-specific phosphorylation of TH
were inhibited by Ca2+/calmodulin-dependent protein kinase (CaMK)
and PKA-specific inhibitors but not by inhibitors of the extracellular
signal-regulated protein kinase pathway, suggesting that IH activates TH in
PC-12 cells via phosphorylation of serine residues including Ser-40, in part,
by CaMK and PKA. Our results also suggest that IH-induced phosphorylation of
TH facilitates the removal of endogenous inhibition of TH, leading to
increased synthesis of dopamine.
recurrent apnea; protein phosphorylation; protein kinase A; Ca2+/calmodulin-dependent protein kinase; catecholamine biosynthesis; PC-12 cells
This article has been cited by other articles:
|
|
 |
|
  D. Souvannakitti, G. K. Kumar, A. Fox, and N. R. Prabhakar Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-Evoked Catecholamine Secretion From Rat Chromaffin Cells J Neurophysiol, June 1, 2009; 101(6): 2837 - 2846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Sharma, G. Raghuraman, M.-S. Lee, N. R. Prabhakar, and G. K. Kumar Intermittent hypoxia activates peptidylglycine {alpha}-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing J Appl Physiol, January 1, 2009; 106(1): 12 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Levy, J-L. Pepin, C. Arnaud, R. Tamisier, J-C. Borel, M. Dematteis, D. Godin-Ribuot, and C. Ribuot Intermittent hypoxia and sleep-disordered breathing: current concepts and perspectives Eur. Respir. J., October 1, 2008; 32(4): 1082 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Murphy, X. Zhang, R. R. Gainetdinov, J.-M. Beaulieu, and M. G. Caron A Regulatory Domain in the N Terminus of Tryptophan Hydroxylase 2 Controls Enzyme Expression J. Biol. Chem., May 9, 2008; 283(19): 13216 - 13224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gozal, Z. A. Shah, J.-M. Pequignot, J. Pequignot, L. R. Sachleben, M. F. Czyzyk-Krzeska, R. C. Li, S.-Z. Guo, and D. Gozal Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia J Appl Physiol, August 1, 2005; 99(2): 642 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gozal, L. R. Sachleben Jr., M. J. Rane, C. Vega, and D. Gozal Mild sustained and intermittent hypoxia induce apoptosis in PC-12 cells via different mechanisms Am J Physiol Cell Physiol, March 1, 2005; 288(3): C535 - C542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Yuan, J. Nanduri, C. R. Bhasker, G. L. Semenza, and N. R. Prabhakar Ca2+/Calmodulin Kinase-dependent Activation of Hypoxia Inducible Factor 1 Transcriptional Activity in Cells Subjected to Intermittent Hypoxia J. Biol. Chem., February 11, 2005; 280(6): 4321 - 4328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cooper, G.-Y. Liu, Y.-L. Niu, S. Santos, L. C. Murphy, and P. H. Watson Intermittent Hypoxia Induces Proteasome-Dependent Down-Regulation of Estrogen Receptor {alpha} in Human Breast Carcinoma Clin. Cancer Res., December 15, 2004; 10(24): 8720 - 8727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yuan, G. Adhikary, A. A. McCormick, John. J. Holcroft, G. K. Kumar, and N. R. Prabhakar Role of oxidative stress in intermittent hypoxia-induced immediate early gene activation in rat PC12 cells J. Physiol., June 15, 2004; 557(3): 773 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Kumar and J. B. Klein Analysis of expression and posttranslational modification of proteins during hypoxia J Appl Physiol, March 1, 2004; 96(3): 1178 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-K. Kim, N. Natarajan, N. R. Prabhakar, and G. K. Kumar Facilitation of dopamine and acetylcholine release by intermittent hypoxia in PC12 cells: involvement of calcium and reactive oxygen species J Appl Physiol, March 1, 2004; 96(3): 1206 - 1215. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
