CREB phosphorylation following hypoxia and ischemia in striatum of newborn piglets: possible role of dopamine.
The goal of the present study was to determine the effects of hypoxia and ischemia and the role of dopamine on phosphorylation of cAMP response element binding protein (CREB) in striatum of newborn piglets. Piglets, with and without prior injection of alpha-methyl-p-tyrosine (AMT), an inhibitor of dopamine (DA) synthesis, were subjected to 1 h of hypoxia (decreased inspired oxygen pressure, FiO2, from 21 to 6%) or 1 h of ischemia (ligation of both carotid arteries and hemorrhage to reduce the systemic arterial pressure to about 40 mmHg), followed by 2 h recovery. Microvascular oxygen pressure in the cortex (pCO2) was measured by quenching of phosphorescence. Extracellular DA was determined by in vivo microdialysis. Striatal levels of phosphorylated CREB (pCREB) and total CREB were determined by Western blots. In sham-operated animals, pCO2 was 49.7 +/- 8.2 mmHg. During hypoxia and ischemia, pCO2 decreased to 6.3 +/- 1.8 mmHg and 10.2 +/- 2.7 mmHg, respectively. There was statistical difference in the level of extracellular DA during hypoxia versus ischemia. At the end of ischemia and hypoxia, the levels of DA were 96 x 10(3) +/- 24 x 10(3)% and 26 x 10(3) +/- 12 x 10(3)% of control, respectively. The pCREB measured after 2 h recovery was not changed after hypoxia but was decreased to 47.8 +/- 24% of control after ischemia. Depletion of endogenous DA abolished the ischemia-induced decrease in pCREB level. Total CREB did not change after either condition. It can be concluded that observed decreases of CREB phosphorylation following ischemia can be at least partially due to the high extracellular DA level.
Zaitseva
Tatiana
T
Department of Biochemistry and Biophysics, School of Medicine, 264 Anatomy Chemistry Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Creed
Jennifer
J
Antoni
Diego
D
Wilson
David F
DF
Pastuszko
Anna
A
D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D010766:Phosphorylation; D013552:Swine
D017362:Cyclic AMP Response Element-Binding Protein; D004298:Dopamine