Effects of Magnesium Sulfate Administration During Hypoxia on CaM Kinase IV and Protein Tyrosine Kinase Activities in the Cerebral Cortex of Newborn Piglets |
| |
Authors: | Ahmed G Mami Juan R Ballesteros Karen I Fritz Joanna Kubin Om P Mishra Maria Delivoria-Papadopoulos |
| |
Institution: | (1) Department of Pediatric Surgery, Drexel University College of Medicine and St. Christopher’s Hospital for Children, Philadelphia, PA, USA;(2) Department of Pediatrics, Temple University, Philadelphia, PA, USA;(3) Department of Pediatrics, Drexel University College of Medicine and St. Christopher’s Hospital for Children, Philadelphia, PA, USA;(4) FRCS (Glasgow), Neonatal Research Laboratory, Drexel University College of Medicine, 3300 Henry Avenue, Philadelphia, PA 19129, USA |
| |
Abstract: | The present study tested the hypothesis that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase
in Ca2+/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 (Mg2+-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 Mg2+-Hx newborn piglets. There was a significant difference between CaM kinase IV activity (pmoles/mg protein/min) in Nx (270 ± 49),
Mg2+-Hx (317 ± 82) and Hx (574 ± 41, P < 0.05 vs. Nx and Mg2+-Hx) groups. Similarly, there was a significant difference between Protein Tyrosine Kinase activity (pmoles/mg protein/h)
in normoxic (378 ± 68), Mg2+-Hx (455 ± 67) and Hx (922 ± 66, P < 0.05 vs. Nx and Mg2+-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 Ca2+-flux, magnesium sulfate administration inhibits the Ca2+/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. |
| |
Keywords: | Ca2+/calmodulin-dependent protein kinase IV Protein Tyrosine Kinase Magnesium sulfate hypoxia |
本文献已被 PubMed SpringerLink 等数据库收录! |
|