A critical role of neural-specific JNK3 for ischemic apoptosis

Chia Yi Kuan; Alan J. Whitmarsh; Derek D. Yang; Guanghong Liao; Aryn J. Schloemer; Chen Dong; Jue Bao; Kenneth J. Banasiak; Gabriel G. Haddad; Richard A. Flavell; Roger J. Davis; Pasko Rakic

doi:10.1073/pnas.2336254100

A critical role of neural-specific JNK3 for ischemic apoptosis

Chia Yi Kuan, Alan J. Whitmarsh, Derek D. Yang, Guanghong Liao, Aryn J. Schloemer, Chen Dong, Jue Bao, Kenneth J. Banasiak, Gabriel G. Haddad, Richard A. Flavell, Roger J. Davis, Pasko Rakic

Immunology

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385 Scopus citations

Abstract

c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.

Original language	English (US)
Pages (from-to)	15184-15189
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	25
DOIs	https://doi.org/10.1073/pnas.2336254100
State	Published - Dec 9 2003

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Kuan, C. Y., Whitmarsh, A. J., Yang, D. D., Liao, G., Schloemer, A. J., Dong, C., Bao, J., Banasiak, K. J., Haddad, G. G., Flavell, R. A., Davis, R. J., & Rakic, P. (2003). A critical role of neural-specific JNK3 for ischemic apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15184-15189. https://doi.org/10.1073/pnas.2336254100

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title = "A critical role of neural-specific JNK3 for ischemic apoptosis",

abstract = "c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.",

author = "Kuan, {Chia Yi} and Whitmarsh, {Alan J.} and Yang, {Derek D.} and Guanghong Liao and Schloemer, {Aryn J.} and Chen Dong and Jue Bao and Banasiak, {Kenneth J.} and Haddad, {Gabriel G.} and Flavell, {Richard A.} and Davis, {Roger J.} and Pasko Rakic",

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doi = "10.1073/pnas.2336254100",

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T1 - A critical role of neural-specific JNK3 for ischemic apoptosis

AU - Kuan, Chia Yi

AU - Whitmarsh, Alan J.

AU - Yang, Derek D.

AU - Liao, Guanghong

AU - Schloemer, Aryn J.

AU - Dong, Chen

AU - Bao, Jue

AU - Banasiak, Kenneth J.

AU - Haddad, Gabriel G.

AU - Flavell, Richard A.

AU - Davis, Roger J.

AU - Rakic, Pasko

PY - 2003/12/9

Y1 - 2003/12/9

N2 - c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.

AB - c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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A critical role of neural-specific JNK3 for ischemic apoptosis

Abstract

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