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Effects of Chemical Ischemia on Cerebral Cortex Slices
Author(s) -
SINISCALCHI ANNA,
CAVALLINI SABRINA,
MARINO SILVIA,
FALZARANO SOFIA,
FRANCESCHETTI LARA,
SELVATICI RITA
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.047
Subject(s) - p38 mitogen activated protein kinases , kinase , mapk/erk pathway , phosphorylation , mitogen activated protein kinase , protein kinase a , ischemia , medicine , endocrinology , chemistry , glutamate receptor , extracellular , biology , biochemistry , receptor
A variety of harmful stimuli, among them energy depletion occurring during transient brain ischemia, are thought to unbalance protein kinase cascades, ultimately leading to neuronal damage. In superfused, electrically stimulated rat cerebral cortex slices, chemical ischemia (CI) was induced by a 5‐min treatment with the mitochondrial toxin, sodium azide (10 mM), combined with the glycolysis blocker, 2‐deoxyglucose (2 mM). Thereafter, 1 h reperfusion (REP) with normal medium followed. Western blot analysis of p21 Ras , extracellular signal‐regulated protein kinases (ERK)1/2 (p44/42), phospho‐ERK1/2, mitogen‐activated protein kinase (MAPK)‐p38, phospho‐p38, stress‐activated protein kinases/c‐Jun NH 2 ‐terminal protein kinases (SAPK/JNK), phospho‐SAPK/JNK was carried out. The level of p21 Ras was increased by 40% immediately after CI, and did not return to control values following REP. Both ERK1 and ERK2 levels were reduced by CI and recovered to control values following REP; no significant change in their phosphorylation degree (phosphorylated to total level ratio, about 50% in the controls) was observed. Neither p38 levels, nor phosphorylation degree were changed following CI/REP. The activation of SAPK/JNK was significantly reduced under CI, and did not recover following REP. All CI/REP‐induced effects were prevented by the NMDA receptor antagonist MK‐801, 10 μM, suggesting the involvement of glutamate. The present findings show that although CI stimulates the p21 Ras protein, MAPK levels and/or phosphorylation are reduced, possibly because of acute energy depletion. Because the activation of SAPK/JNK has been related to both apoptosis and neuroprotection, the decrease observed under CI/REP conditions may instead be related to nonapoptotic neuronal death. These results could be of interest in developing preventive treatments for ischemia/REP‐induced brain damage.