Effects of magnesium sulfate administration during hypoxia on CaM kinase IV and protein tyrosine kinase activities in the cerebral cortex of newborn piglets.
The present study tested the hypothesis that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase in Ca(2+)/Calmodulin-dependent-kinase (CaM Kinase) IV and Protein Tyrosine Kinase (PTK ) activities. Animals were randomly divided into normoxic (Nx), hypoxic (Hx) and magnesium-pretreated hypoxic (Mg(2+)-Hx) groups. Cerebral hypoxia was confirmed biochemically by measuring ATP and phosphocreatine (PCr) levels. CaM Kinase IV and PTK activities were determined in Nx, Hx and Mg(2+)-Hx newborn piglets. There was a significant difference between CaM kinase IV activity (pmoles/mg protein/min) in Nx (270 +/- 49), Mg(2+)-Hx (317 +/- 82) and Hx (574 +/- 41, P < 0.05 vs. Nx and Mg(2+)-Hx) groups. Similarly, there was a significant difference between Protein Tyrosine Kinase activity (pmoles/mg protein/h) in normoxic (378 +/- 68), Mg(2+)-Hx (455 +/- 67) and Hx (922 +/- 66, P < 0.05 vs. Nx and Mg(2+)-Hx ) groups. We conclude that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase in CaM Kinase IV and Protein Tyrosine Kinase activities. We propose that by blocking the NMDA receptor ion-channel mediated Ca(2+)-flux, magnesium sulfate administration inhibits the Ca(2+)/calmodulin-dependent activation of CaMKIV and prevents the generation of nitric oxide free radicals and the subsequent increase in PTK activity. As a result, phosphorylation of CREB and Bcl-2 family of proteins is prevented leading to prevention of programmed cell death.
Department of Pediatric Surgery, Drexel University College of Medicine and St. Christopher's Hospital for Children, Philadelphia, PA 19129, USA. agmami@yahoo.com
Ahmed G
AG
Mami
Juan R
JR
Ballesteros
Karen I
KI
Fritz
Joanna
J
Kubin
Om P
OP
Mishra
Maria
M
Delivoria-Papadopoulos
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000378:metabolism*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002458:Cell Fractionation; D002540:Cerebral Cortex / Q000201:enzymology*; D000860:Hypoxia / Q000378:metabolism*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013552:Swine
D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D010725:Phosphocreatine; D008278:Magnesium Sulfate; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases