Magnesium blocks the loss of protein kinase C, leads to a transient translocation of PKC(alpha) and PKC(epsilon), and improves recovery after anoxia in rat hippocampal slices.
Magnesium is a potent neuroprotective agent against damage to synaptic transmission during cerebral anoxia and reoxygenation. We investigated the mechanisms of anoxic transmission damage and magnesium neuroprotection by examining the response of PKC isoforms to an anoxic insult in the rat hippocampal slice model. A 2-min anoxic period, which resulted in almost complete recovery of synaptic function, did not result in PKC downregulation. In contrast, inducing long-term damage with 10-min anoxia resulted in the downregulation of the conventional PKCs betaI, betaII and gamma immediately after the insult and after 1-h reoxygenation. There was additional loss of PKC(alpha) and PKC(epsilon) after 1-h reoxygenation. Magnesium treatment improved the recovery of synaptic transmission, blocked the loss of PKC and resulted in a transient translocation of PKC(alpha) and PKC(epsilon) to the membrane fraction. Selective downregulation of cPKCs and PKC(epsilon) correlated with permanent damage to synaptic transmission while translocation of PKC(alpha) and PKC(epsilon) correlated with preservation of synaptic function. The mechanisms of magnesium neuroprotection may include altering the PKC response to an anoxic insult.
Libien
Jenny
J
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Sacktor
Todd Charlton
TC
Kass
Ira S
IS
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D006624:Hippocampus / Q000187:drug effects*; D000860:Hypoxia / Q000188:drug therapy; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology* / Q000627:therapeutic use; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D021381:Protein Transport / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
C497257:Prkce protein, rat; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D008274:Magnesium