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Titolo:
Inhibition of cyclic AMP-dependent protein kinase in the acute phase of focal cerebral ischemia in the rat
Autore:
Tanaka, K; Nogawa, S; Nagata, E; Suzuki, S; Dembo, T; Kosakai, A; Fukuuchi, Y;
Indirizzi:
Keio Univ, Sch Med, Dept Neurol, Tokyo 1608582, Japan Keio Univ Tokyo Japan 1608582 Sch Med, Dept Neurol, Tokyo 1608582, Japan
Titolo Testata:
NEUROSCIENCE
fascicolo: 2, volume: 94, anno: 1999,
pagine: 361 - 371
SICI:
0306-4522(1999)94:2<361:IOCAPK>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARTERY OCCLUSION; BLOOD-FLOW; REGULATORY SUBUNIT; ENERGY-STATE; BRAIN-DAMAGE; GERBIL BRAIN; BINDING; PHOSPHORYLATION; LOCALIZATION; MODEL;
Keywords:
cyclic AMP; cyclic AMP-dependent protein kinase; PKA; cerebral ischemia; focal ischemia; signal transduction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Tanaka, K Keio Univ, Sch Med, Dept Neurol, Tokyo 1608582, Japan Keio UnivTokyo Japan 1608582 ept Neurol, Tokyo 1608582, Japan
Citazione:
K. Tanaka et al., "Inhibition of cyclic AMP-dependent protein kinase in the acute phase of focal cerebral ischemia in the rat", NEUROSCIENC, 94(2), 1999, pp. 361-371

Abstract

Binding of cyclic AMP to the regulatory subunit of cyclic AMP-dependent protein kinase is an essential step in cyclic AMP-mediated intracellular signal transduction. In the present study, the binding capacity of cyclic AMP-dependent protein kinase for cyclic AMP was examined by autoradiography withlocal cerebral blood flow in focal cerebral ischemia in the rat, which wasinduced by occlusion of the middle cerebral artery using the intraluminal suture method. The binding capacity of cyclic AMP-dependent protein kinase and local cerebral blood flow were assessed by the in vitro [H-3]cyclic AMPbinding and the [C-14]iodoantipyrine methods, respectively. At 3 h of occlusion, a significant reduction in the binding of cyclic AMP-dependent protein kinase to cyclic AMP was already noted in the lateral region of the caudate-putamen and the parietal cortex. Between three and five hours of occlusion, the area with reduced cyclic AMP binding was significantly expanded tothe peri-ischemic regions including the frontal cortex and the medial region of the caudate-putamen. The threshold in local cerebral blood flow for reduced cyclic AMP binding was clearly noted at 5 h of ischemia, and was 45 ml/100 g per min in the cerebral cortices, and 38 ml/100 g per min in the caudate-putamen, respectively. No threshold was noted at 3 h of ischemia, since cyclic AMP binding showed a large variation ranging from reduced to normal values even when local cerebral blood flow was below 20 ml/100 g per min. Recirculation for 3.5 h following 1.5 h of ischemia restored the normal cyclic AMP binding in the cerebral cortices, but failed to normalize cyclicAMP binding in the caudate-putamen despite good recovery of local cerebralblood flow. Western blot analysis suggested that this reduction in cyclic AMP binding was not due to loss or degradation of the subunit protein of cyclic AMP-dependent protein kinase, and may therefore have resulted from conformational changes in the protein. A significant increase in cyclic AMP binding was noted after recirculation in the non-ischemic regions such as thefrontal and the cingulate cortices on the occluded side and in the contralateral cortices. These data indicate that cyclic AMP-mediated signal transduction in the brain tissue may be very susceptible to ischemic stress, and the region of disrupted signal transduction may expand progressively from the ischemic coreto peri-ischemic regions in the acute phase of ischemia. Such impairment of signal transduction may not be restored in the caudate-putamen even when cerebral circulation is fully recovered after short-term ischemia, suggesting that a regional vulnerability to ischemic stress may also exist in cyclic AMP-mediated signal transduction. A significant increase in cyclic AMP binding after recirculation in regions outside of ischemic area may be closely related with the protective mechanisms of brain tissue, since cyclic AMP has been reported to exert various neuroprotective actions. (C) 1999 IBRO. Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 22:38:42