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Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia.
Acta Neuropathol 2003; 105(5):425-37AN

Abstract

Focal ischemia induced by middle cerebral artery occlusion (MCAO) to adult rats results in necrosis at the infarct core and activation of complex signal pathways for cell death and cell survival in the penumbra. Upstream from the cell death promoters and executioners are several kinases that, once activated by phosphorylation, may activate several transcription factor substrates involved in cell death and cell survival. In the present study we examined, by immunohistochemistry, the expression of phosphorylated (active) mitogen-activated protein kinase, extracellular signal-regulated kinase (MAPK/ERK), stress-activated protein kinase (SAPK), c-Jun N-terminal kinase (JNK) and p-38 kinase at early stages (1-4 h) following 1 h of MCAO in the rat. The expression of phosphorylation-dependent, active transcription substrates of these kinases, including cyclic AMP-responsive element-binding protein (CREB) Alk-1, ATF-2, c-Myc and c-Jun was examined at early stages following reperfusion. Increased nuclear phosphorylated SAPK/JNK (SAPK/JNK-P) and c-Jun-PSer63, and reduced CREB-P, occurred in the infarct core at 1 h following reperfusion, suggesting increased phosphorylated SAPK/JNK and c-JunSer63, together with decreased phospho-CREB associated with cell death in the infarct core. However, increased cytoplasmic expression of MAPK/ERK-P, SAPK/JNK-P, p38-P, CREB-P, Elk-1-P, c-Myc-P, ATF-2-P and c-Jun-P occurred in the region bordering the infarct core (penumbra) at 4 h following reperfusion. This indicates that different signals converge in the cytoplasm of neurons located at the borders of the infarct at 4 h following reperfusion, revealing the struggle of death promoters and life facilitators at the penumbra. Whether phosphorylated kinases and specific substrates participate in promoting cell death or survival in the penumbra probably depends on additional factors and on the interaction with other proteins.

Authors+Show Affiliations

Institut de Neuropatologia, Servei d'Anatomia Patològica, Hospital Princeps d'Espanya, Universitat de Barcelona, Campus de Bellvitge, carrer Feixa LLarga sn, 08907 Hospitalet de Llobregat, Spain. 8082ifa@comb.esNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12677442

Citation

Ferrer, I, et al. "Early Modifications in the Expression of Mitogen-activated Protein Kinase (MAPK/ERK), Stress-activated Kinases SAPK/JNK and P38, and Their Phosphorylated Substrates Following Focal Cerebral Ischemia." Acta Neuropathologica, vol. 105, no. 5, 2003, pp. 425-37.
Ferrer I, Friguls B, Dalfó E, et al. Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathol. 2003;105(5):425-37.
Ferrer, I., Friguls, B., Dalfó, E., & Planas, A. M. (2003). Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathologica, 105(5), pp. 425-37.
Ferrer I, et al. Early Modifications in the Expression of Mitogen-activated Protein Kinase (MAPK/ERK), Stress-activated Kinases SAPK/JNK and P38, and Their Phosphorylated Substrates Following Focal Cerebral Ischemia. Acta Neuropathol. 2003;105(5):425-37. PubMed PMID: 12677442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. AU - Ferrer,I, AU - Friguls,B, AU - Dalfó,E, AU - Planas,A M, Y1 - 2003/01/21/ PY - 2002/10/08/received PY - 2002/11/04/accepted PY - 2003/4/5/pubmed PY - 2003/6/7/medline PY - 2003/4/5/entrez SP - 425 EP - 37 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 105 IS - 5 N2 - Focal ischemia induced by middle cerebral artery occlusion (MCAO) to adult rats results in necrosis at the infarct core and activation of complex signal pathways for cell death and cell survival in the penumbra. Upstream from the cell death promoters and executioners are several kinases that, once activated by phosphorylation, may activate several transcription factor substrates involved in cell death and cell survival. In the present study we examined, by immunohistochemistry, the expression of phosphorylated (active) mitogen-activated protein kinase, extracellular signal-regulated kinase (MAPK/ERK), stress-activated protein kinase (SAPK), c-Jun N-terminal kinase (JNK) and p-38 kinase at early stages (1-4 h) following 1 h of MCAO in the rat. The expression of phosphorylation-dependent, active transcription substrates of these kinases, including cyclic AMP-responsive element-binding protein (CREB) Alk-1, ATF-2, c-Myc and c-Jun was examined at early stages following reperfusion. Increased nuclear phosphorylated SAPK/JNK (SAPK/JNK-P) and c-Jun-PSer63, and reduced CREB-P, occurred in the infarct core at 1 h following reperfusion, suggesting increased phosphorylated SAPK/JNK and c-JunSer63, together with decreased phospho-CREB associated with cell death in the infarct core. However, increased cytoplasmic expression of MAPK/ERK-P, SAPK/JNK-P, p38-P, CREB-P, Elk-1-P, c-Myc-P, ATF-2-P and c-Jun-P occurred in the region bordering the infarct core (penumbra) at 4 h following reperfusion. This indicates that different signals converge in the cytoplasm of neurons located at the borders of the infarct at 4 h following reperfusion, revealing the struggle of death promoters and life facilitators at the penumbra. Whether phosphorylated kinases and specific substrates participate in promoting cell death or survival in the penumbra probably depends on additional factors and on the interaction with other proteins. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/12677442/Early_modifications_in_the_expression_of_mitogen_activated_protein_kinase__MAPK/ERK__stress_activated_kinases_SAPK/JNK_and_p38_and_their_phosphorylated_substrates_following_focal_cerebral_ischemia_ L2 - https://dx.doi.org/10.1007/s00401-002-0661-2 DB - PRIME DP - Unbound Medicine ER -