Alteration of protein kinase C activity in the postischemic rat brain areas using in vitro [3H]phorbol 12,13-dibutyrate autoradiography.
Chronological changes of protein kinase C (PKC) activity were measured using in vitro [3H]phorbol 12,13-dibutyrate (PDBu) autoradiography to investigate the postischemic alteration of this second messenger system in the rat brain. Transient ischemia was induced by the occlusion of the middle cerebral artery (MCA) for 90 min and such occlusion followed by various recirculation periods of up to 4 weeks. After 90 min of ischemia followed by 3 hours of recirculation, [3H]PDBu binding sites were found to be significantly decreased in the cerebral cortex and lateral segment of the caudate putamen, both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, a significant decrease of [3H]PDBu binding sites was first detected in the ipsilateral thalamus and the substantia nigra, which both areas had not been directly affected by the original ischemic insult. This postischemic delayed phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. These results suggest that alteration of second messenger (PKC) pathways may be involved not only in the ischemic foci, but also in neuronal degeneration of the exo-focal remote areas in relation to the disruption of intracellular calcium homeostasis which plays a key role in the pathogenesis of postischemic neuronal damage and that marked alteration of intracellular signal transduction may precede the neuronal damage in the exo-focal postischemic brain areas.
Nagasawa
H
H
Department of Neurology, Institute of Brain Diseases, Tohoku University School of Medicine, Sendai, Japan.
Araki
T
T
Kogure
K
K
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002536:Cerebral Arteries / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000473:pathology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000502:physiology; D013997:Time Factors
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C