Neurochemical Research

, Volume 31, Issue 1, pp 57–62

Effects of Magnesium Sulfate Administration During Hypoxia on CaM Kinase IV and Protein Tyrosine Kinase Activities in the Cerebral Cortex of Newborn Piglets

  • Ahmed G. Mami
  • Juan R. Ballesteros
  • Karen I. Fritz
  • Joanna Kubin
  • Om P. Mishra
  • Maria Delivoria-Papadopoulos
Article

DOI: 10.1007/s11064-005-9135-y

Cite this article as:
Mami, A.G., Ballesteros, J.R., Fritz, K.I. et al. Neurochem Res (2006) 31: 57. doi:10.1007/s11064-005-9135-y

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.

Key words:

Ca2+/calmodulin-dependent protein kinase IV Protein Tyrosine Kinase Magnesium sulfate hypoxia 

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Ahmed G. Mami
    • 1
    • 4
  • Juan R. Ballesteros
    • 2
  • Karen I. Fritz
    • 3
  • Joanna Kubin
    • 3
  • Om P. Mishra
    • 3
  • Maria Delivoria-Papadopoulos
    • 3
  1. 1.Department of Pediatric SurgeryDrexel University College of Medicine and St. Christopher’s Hospital for ChildrenPhiladelphiaUSA
  2. 2.Department of PediatricsTemple UniversityPhiladelphiaUSA
  3. 3.Department of PediatricsDrexel University College of Medicine and St. Christopher’s Hospital for ChildrenPhiladelphiaUSA
  4. 4.FRCS (Glasgow), Neonatal Research LaboratoryDrexel University College of MedicinePhiladelphiaUSA

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