Opposite reaction of ERK and JNK in ischemia vulnerable and resistant regions of hippocampus: involvement of mitochondria

Zabłocka, Barbara; Dużniewska, Joanna; Zajac, H; Domańska-Janik, Krystyna

doi:10.1016/s0169-328x(02)00653-8

Cited by 37 publications

(27 citation statements)

References 37 publications

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“…However, there is some inconsistency in the temporospatial distribution of phospho-c-Jun and phospho-JNK expression (Ferrer et al, 2003;Zablocka et al, 2003). It has also been reported that an increase in phospho-c-Jun levels was detected after 5 min of global ischemia without an increase in phospho-JNK levels (Gillardon et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia

Okuno

Saito²,

Hayashi³

et al. 2004

J. Neurosci.

226

148

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The c-Jun N-terminal protein kinase (JNK) signaling pathway is implicated in neuronal apoptosis. The mechanism by which activated JNK induces neuronal apoptosis is strongly linked to mitochondrial apoptogenic proteins, although the molecular machinery downstream of JNK has not been precisely elucidated. Our study examined the relevance of proapoptotic Bcl-2 family members in JNKmediated apoptosis after transient focal cerebral ischemia (tFCI), which, when induced by 60 min of middle cerebral artery (

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Section: Discussionmentioning

confidence: 99%

The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia

Okuno

Saito²,

Hayashi³

et al. 2004

J. Neurosci.

226

148

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“…JNKs trigger neuropathological events, e.g. after trophic support withdrawal in sympathetic neurons (2)(3)(4) or cerebellar neurons (5,6), delayed ischemic cell death (7), excitotoxicity (8), or in models for Alzheimer's disease (9) and Parkinson's disease (10 -13). The modes of degeneration mediated by JNKs, however, are far from being completely understood.…”

mentioning

confidence: 99%

“…Bim (4,17), in the nucleus. The JNKmediated mitochondrial pathology was reported following growth factor withdrawal in cerebellar granule cells (4,26,27,31), amyloid ␤-induced neurodegeneration (9,32), or cerebral ischemia (7).…”

mentioning

confidence: 99%

JNK2 Translocates to the Mitochondria and Mediates Cytochrome c Release in PC12 Cells in Response to 6-Hydroxydopamine

Eminel¹,

Klettner²,

Roemer³

et al. 2004

Journal of Biological Chemistry

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6-Hydroxydopamine (6-OHDA) causes death of dopaminergic neurons by mitochondrial dysfunction with JNKs as central mediators. Here we provide novel insights into specific actions of JNK isoforms in 6-OHDAinduced death of PC12 cells. Twenty five M 6-OHDA enhanced total JNK activity in the cytoplasm, nucleus, and at the mitochondria. Inhibition of JNKs by 2 M SP600125 or transfection with dominant-negative JNK2 (dnJNK2) rescued more than 60% of the otherwise dying PC12 cells after 24 h, whereas transfection with dnJNK1 had no protective effects. In contrast to constitutively present JNK1, JNK2 amounts increased in the nucleus and at the mitochondria after 6-OHDA stimulation. JNK inhibition by SP600125 or transfection of dnJNK2 reduced the pool of active JNKs in the nucleus, the release of cytochrome c, as well as the cleavage of caspase-3 and its substrate poly(ADP-ribose) polymerase-1. Transfection with dnJNK1, however, had no effects on the translocation of JNKs to the mitochondria or the release of cytochrome c. Our data provide novel functional insights into the pathological role of individual JNK isoforms, the signalosome at the mitochondria, and the mode of JNK-induced release of cytochrome c.

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“…ERK signalling is primarily activated by mitogens such as growth factors, phorbol esters and serum (Rossler et al, 2004;Hetman et al, 1999;Gause et al, 1993;Whitmarsh et al, 1995) but can also be stimulated by various cell stressors (Lewis et al, 1998;Ji et al, 1999). Phosphorylated ERK is found to a greater degree in the penumbra than in the ischemic core (Irving et al, 2000;Ferrer and Planas, 2003) and crucially is present at much higher levels in ischemia resistant regions of the hippocampus (Gu et al, 2001;Zablocka et al, 2003). Hypothermic neuroprotection also coincides with ERK activation (Hicks et al, 2000) and taken together this body of evidence generally supports a protective role for ERK signalling.…”

Section: Discussionmentioning

confidence: 99%

Injury-induced mineralocorticoid receptor expression involves differential promoter usage: A novel role for the rat MRβ variant

Kang

Rogalska

Walker

et al. 2009

Molecular and Cellular Endocrinology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Neuronal injury results in increased mineralocorticoid receptor (MR) expression and is associated with increased neuronal survival, suggesting that enhancing MR signalling may have therapeutic implications. MR has a complex gene structure with at least three untranslated exons (α, β, γ) each with unique promoters and a common coding region. We examined whether distinct cellular stressors differentially regulate exon-specific MR transcripts. MRβ transcript was specifically upregulated in rat primary cortical cultures undergoing hypothermic oxygen-glucose deprivation (OGD/H) through activation of its own promoter. This effect was mediated in part by ERK signalling as blockade with PD98059 inhibited OGD/H-induced MRβ promoter activity. A specific increase in MRβ transcript expression was also found in vivo in hypothermic anoxic neonatal rat hippocampus. These results demonstrate a novel key role for the MRβ transcript in response to injury and suggest that some of the known neuroprotective effects of hypothermia may be mediated through increased MR expression.

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Opposite reaction of ERK and JNK in ischemia vulnerable and resistant regions of hippocampus: involvement of mitochondria

Cited by 37 publications

References 37 publications

The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia

The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia

JNK2 Translocates to the Mitochondria and Mediates Cytochrome c Release in PC12 Cells in Response to 6-Hydroxydopamine

Injury-induced mineralocorticoid receptor expression involves differential promoter usage: A novel role for the rat MRβ variant

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