Spinal cord ischemia reduces calcium/calmodulin-dependent protein kinase activity.
Calcium/calmodulin (Ca2+/CaM)-dependent protein phosphorylation was evaluated in a rabbit spinal cord ischemia model. One hour of ischemia reduced particulate (5% of control) and cytosolic (35% of control) Ca2+/CaM-dependent protein kinase activity significantly (p less than 0.01). In vitro phosphorylation of endogenous proteins by endogenous Ca2+/CaM-dependent protein kinase showed that phosphorylation of 14 particulate and 7 cytosolic proteins was stimulated in the presence of Ca2+/CaM in control tissue. However, after 1 hour of ischemia, Ca2+/CaM-dependent protein phosphorylation was virtually absent in the particulate fraction and significantly reduced in the cytosol. When equal amounts of control and ischemic tissue samples were combined and assayed, Ca2+/CaM-dependent protein kinase activity was 43% of control in particulate and 70% of control in cytosolic fractions. This suggests that reduced Ca2+/CaM-dependent protein phosphorylation is probably not due to the presence of an inhibitory activity in ischemic tissue. These results show that the Ca2+/CaM-dependent protein phosphorylation system is impaired after ischemia durations which cause irreversible damage. These altered phosphorylation reactions may play critical roles in mediating irreversible neurologic injury.
Kochhar
A
A
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093.
Saitoh
T
T
Zivin
J A
JA
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003600:Cytosol / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology* / Q000378:metabolism; D008161:Lumbosacral Region; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply*
D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases