title: Calcium-dependent protein kinase C activation in acutely isolated neurons during oxygen and glucose deprivation.
abstract: Glutamate excitotoxicity and necrotic cell death are characteristic features of ischemic neuronal injury. In the penumbral area, glutamate exposure is less pronounced and neuronal death is delayed. Recent studies suggest that delayed neuronal death is propagated by intracellular signalling pathways. Protein kinase C (PKC) activation may initiate apoptosis, but its role in ischemia is still not clear. In this study the PKC activity was investigated during non-excitotoxic ischemia in acutely dissociated rat CA1 neurons. During oxygen and glucose deprivation (OGD) the PKC activity measured with the fluorescent dye Fim-1 increased rapidly reaching a maximum of 31+/-8% (P < 0.05) after 5 min. When extracellular Ca2+ was depleted, the fluorescence intensity increased by 20+/-8% (P<0.05), but with a slower onset. In neurons treated with thapsigargin in a Ca2+ depleted solution, however, OGD did not trigger PKC activation. The results suggest that the PKC activation is mainly triggered by Ca2+ release from endogenous stores.
authors.affiliation: Institute for Surgical Research and Department of Neurosurgery, National Hospital, Rikshospitalet, 0027 Oslo, Norway. g.a.larsen@labmed.uio.no
authors.forename: Geir Arne
authors.initials: GA
authors.lastname: Larsen
authors.forename: Jon
authors.initials: J
authors.lastname: Berg-Johnsen
authors.forename: Morten C
authors.initials: MC
authors.lastname: Moe
authors.forename: Morten Larsen
authors.initials: ML
authors.lastname: Vinje
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002469:Cell Separation / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011493:Protein Kinase C; D005947:Glucose; D010100:Oxygen