Modulation of ERK and JNK activity by transient forebrain ischemia in rats

Shackelford, Deborah A.; Yeh, Richard

doi:10.1002/jnr.20747

Cited by 26 publications

(19 citation statements)

References 64 publications

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“…10,[28][29][30][31] We confirmed that ERK1/2 and JNK signaling were activated during hypoxia and following reoxygenation. 32, 33 We further found that SsnB indeed suppressed the activation of these two pathways during hypoxia and reoxygenation.…”

Section: Discussionsupporting

confidence: 87%

Sparstolonin B attenuates hypoxia–reoxygenation-induced cardiomyocyte inflammation

Liu

Wang

Liang

et al. 2014

Exp Biol Med (Maywood)

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Myocardial ischemia-reperfusion (MIR) injury is characterized by a rapid increase in cytokines and chemokines and an infiltration of inflammatory cells. Toll-like receptors (TLRs) 2 and 4 mediate these inflammatory responses. Herein we investigated the ability of Sparstolonin B (SsnB), a new selective TLR2/4 antagonist, to inhibit the TLR2/4-mediated inflammatory responses during cardiomyocyte hypoxia-reoxygenation injury as well as the responsible mechanisms. Lactate dehydrogenase (LDH) assay was performed to measure the cytotoxicity of SsnB on H9c2 cardiomyocytes. Quantitative real-time PCR (qRT-PCR) confirmed that TLR2 and TLR4 expression was elevated during hypoxia-reoxygenation, and that their up-regulation in cardiomyocytes was significantly inhibited by SsnB (P < 0.05). Both the mRNA and protein levels of monocyte chemotactic protein-1 and high mobility group box 1 were up-regulated during hypoxia-reoxygenation and were significantly attenuated by SsnB (P < 0.05). Next we found that extracellular signal-regulated kinase 1 or 2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK) signaling pathways were activated during hypoxia-reoxygenation and SsnB significantly inhibited their activation (P < 0.05). Moreover, transwell migration assays revealed that the migration of mouse macrophages to hypoxia-reoxygenation injured cardiomyocytes was significantly reduced by SsnB (P < 0.05). In conclusion, our data indicate that the new selective TLR2 and TLR4 antagonist, SsnB, can substantially attenuate hypoxia-reoxygenation-induced inflammation of cardiomyocytes via inhibiting ERK1/2 and JNK signaling pathways. Accordingly, SsnB has the potential to serve as a therapeutic agent for the prevention of MIR injury.

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Section: Discussionsupporting

confidence: 87%

Sparstolonin B attenuates hypoxia–reoxygenation-induced cardiomyocyte inflammation

Liu

Wang

Liang

et al. 2014

Exp Biol Med (Maywood)

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“…The inset shows that this dose of tautomycin has no effect on LTD in control slices. postischemic brain, the level of phosphorylated, activated ERK1/2 and JNKs was reported to rapidly increase (Farrokhnia et al, 2005;Shackelford and Yeh, 2006), and inhibition of ERK1/2 or JNKs suppresses neuronal injury after transient or permanent MCAO in the rat (Alessandrini et al, 1999;Borsello et al, 2003). However, the actual pathways linking the initial steps of excitotoxicity to ERK/JNK activation and apoptotic processes remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Protein Phosphatase 1-Dependent Bidirectional Synaptic Plasticity Controls Ischemic Recovery in the Adult Brain

Hédou¹,

Koshibu²,

Farinelli³

et al. 2008

J. Neurosci.

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Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/ survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair.

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“…JNK1 and JNK2 are expressed in all tissues and are required for normal brain development. Furthermore, JNK1 displays constitutive activity in the CNS and is required to maintain microtubule integrity in axons and dendrites in the adult animal [272]. In contrast, JNK3 is specifically implicated in promoting neuronal cell death, in that targeted deletion of JNK3 protects mice from brain injury after cerebral ischemiahypoxia [273].…”

Section: C-jun N-terminal Kinase-mediated Apoptosismentioning

confidence: 98%

Molecular Mechanisms of Apoptosis in Cerebral Ischemia: Multiple Neuroprotective Opportunities

et al. 2007

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Cerebral ischemia/reperfusion (I/R) injury triggers multiple and distinct but overlapping cell signaling pathways, which may lead to cell survival or cell damage. There is overwhelming evidence to suggest that besides necrosis, apoptosis do contributes significantly to the cell death subsequent to I/R injury. Both extrinsic and intrinsic apoptotic pathways play a vital role, and upon initiation, these pathways recruit downstream apoptotic molecules to execute cell death. Caspases and Bcl-2 family members appear to be crucial in regulating multiple apoptotic cell death pathways initiated during I/R. Similarly, inhibitor of apoptosis family of proteins (IAPs), mitogen-activated protein kinases, and newly identified apoptogenic molecules, like second mitochondrial-activated factor/direct IAP-binding protein with low pI (Smac/Diablo), omi/high-temperature requirement serine protease A2 (Omi/HtrA2), X-linked mammalian inhibitor of apoptosis protein-associated factor 1, and apoptosis-inducing factor, have emerged as potent regulators of cellular apoptotic/antiapoptotic machinery. All instances of cell survival/death mechanisms triggered during I/R are multifaceted and interlinked, which ultimately decide the fate of brain cells. Moreover, apoptotic cross-talk between major subcellular organelles suggests that therapeutic strategies should be optimally directed at multiple targets/mechanisms for better therapeutic outcome. Based on the current knowledge, this review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators and their emerging roles in orchestrating cell death programme. In addition, we have also highlighted the role of autophagy in modulating cell survival/death during cerebral ischemia. Furthermore, an attempt has been made to provide an encouraging outlook on emerging therapeutic approaches for cerebral ischemia.

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Modulation of ERK and JNK activity by transient forebrain ischemia in rats

Cited by 26 publications

References 64 publications

Sparstolonin B attenuates hypoxia–reoxygenation-induced cardiomyocyte inflammation

Sparstolonin B attenuates hypoxia–reoxygenation-induced cardiomyocyte inflammation

Protein Phosphatase 1-Dependent Bidirectional Synaptic Plasticity Controls Ischemic Recovery in the Adult Brain

Molecular Mechanisms of Apoptosis in Cerebral Ischemia: Multiple Neuroprotective Opportunities

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