Regulation of mitogen‐activated protein kinases by glutamate receptors

Wang, John Q.; Fibuch, Eugene E.; Mao, Limin

doi:10.1111/j.1471-4159.2006.04208.x

Cited by 218 publications

(188 citation statements)

References 106 publications

(203 reference statements)

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“…A large number of studies have documented a profound increase in activated ERK in response to pharmacological activation of NMDA receptors on neurons [56][57][58]. As for mechanisms transmitting NMDA receptor signals to MAPKs, there is a Ca 2+ -sensitive pathway associated with this activity [56][57][58][59].…”

Section: Discussionmentioning

confidence: 99%

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Kanungo

Cuevas

Ali

et al. 2012

Reproductive Toxicology

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Ketamine, an antagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, is a pediatric anesthetic. Ketamine has been shown to be neurotoxic and cardiotoxic in mammals. Here, we show that after 2 h of exposure, 5 mM ketamine significantly reduced heart rate in 26 h old zebrafish embryos. In 52 h old embryos, 1 mM ketamine was effective after 2 h and 0.5 mM ketamine at 20 h of exposure. Ketamine also induced significant reductions in activated MAPK (ERK) levels. Treatment of the embryos with the ERK inhibitor, PD 98059, also significantly reduced heart rate whereas the p38/SAPK inhibitor, SB203580, was ineffective. Ketamine is known to inhibit lipolysis and a decrease of ATP content in the heart. Co-treatment with Lcarnitine that enhances fatty acid metabolism effectively rescued ketamine-induced attenuated heart rate and ERK activity. These findings demonstrate that L-carnitine counteracts ketamine's negative effects on heart rate and ERK activity in zebrafish embryos.

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Section: Discussionmentioning

confidence: 99%

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Kanungo

Cuevas

Ali

et al. 2012

Reproductive Toxicology

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“…MAPK is the primary intracellular signaling cascade that is activated by NMDAR phosphorylation [62]. In this study, ovx, E 2 -primed rats were administered P 4 systemically (100 or 250 μg; SC) and then were infused with a MAPK (MEK-ERK) inhibitor, PD98059 (3 μg/side; dissolved in 10% DMSO) or vehicle, bilaterally to the VTA.…”

Section: Other Downstream Targets Of Progestins In the Vta-nmdars Andmentioning

confidence: 99%

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

Frye

Walf

2008

Steroids

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In the ventral tegmental area (VTA), progestins facilitate lordosis via rapid actions at membrane dopamine Type 1-like (D 1 ) and/or GABA A receptors (GBRs), rather than via cognate, intracellular progestin receptors. Downstream signal transduction pathways involved in these effects were investigated using lordosis as a bioassay. If progestins' actions at D 1 and/or GBRs in the VTA require activation of G-proteins, adenylyl cyclase, cyclic AMP-dependent protein kinase A (PKA), phospholipase C (PLC), and/or PKC, then pharmacologically blocking these pathways would be expected to attenuate progestin-facilitated lordosis and its enhancement by D 1 and GBR activity. Ovariectomized, estradiol-primed rats were infused first with vehicle or signal transduction inhibitor, and second with vehicle, a D 1 or GBR agonist, and then with vehicle or progestins to the VTA. Rats were tested for lordosis following infusions. Results indicated that initiation of G-proteins, adenylyl cyclase, PKA, PLC, or PKC in the VTA is required for rapid effects of progestins through D 1 and/ or GBRs to facilitate lordosis. As well, progestins' actions at n-methyl-d-aspartate receptors (NMDARs) may modulate activity at D 1 and/or GBRs and mitogen activated protein kinase may be a common signaling pathway. Findings from a microarray study demonstrated that there was upregulation of genes associated with steroid metabolism, GBRs, D 1 , NMDARs and signal transduction factors in the midbrain VTA of naturally-receptive mated compared to non-mated rats. Thus, in the VTA, progestins have rapid membrane-mediated actions via D 1 , GBRs, NMDARs and their downstream signal transduction pathways.

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“…Ischemic preconditioning might induce tolerance either by lowering excessive glutamate release or by increasing glutamate uptake (Romera et al, 2007). Activation of glutamate receptors causes calcium influx, activates calcium/CaM kinase, PI3K-Akt pathway, and Ras-MAPK cascade (Soriano et al, 2006;Wang et al, 2007), and in turn converge on CREB activation and upregulation of its target genes. Also, NR2A-containing synaptic NMDA receptors activate the extracellular signal-regulated kinase (ERK) pathway (Leveille et al, 2008).…”

Section: Nr2a Receptors In Ischemic Tolerancementioning

confidence: 99%

Activation of NR2A Receptors Induces Ischemic Tolerance through CREB Signaling

Terasaki

Sasaki

Yagita

et al. 2010

J Cereb Blood Flow Metab

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Previous exposure to a nonlethal ischemic insult protects the brain against subsequent harmful ischemia. N-methyl-D-aspartate (NMDA) receptors are a highly studied target of neuroprotection after ischemia. Recently, NMDA receptor subtypes were implicated in neuronal survival and death. We focused on the contribution of NR2A and cyclic-AMP response element (CRE)-binding protein (CREB) signaling to ischemic tolerance using primary cortical neurons. Ischemia in vitro was modeled by oxygen-glucose deprivation (OGD). Ischemic tolerance was induced by applying 45-mins OGD 24 h before 180-mins OGD. Sublethal OGD also induced cross-tolerance against lethal glutamate and hydrogen peroxide. After sublethal OGD, expression of phosphorylated CREB and CRE transcriptional activity were significantly increased. When CRE activity was inhibited by CREB-S133A, a mutant CREB, ischemic tolerance was abolished. Inhibiting NR2A using NVP-AAM077 attenuated preconditioning-induced neuroprotection and correlated with decreased CRE activity levels. Activating NR2A using bicuculline and 4-aminopiridine induced resistance to lethal ischemia accompanied by elevated CRE activity levels, and this effect was abolished by NVP-AAM077. Elevated brain-derived neurotrophic factor (BDNF) transcriptional activities were observed after sublethal OGD and administration of bicuculline and 4-aminopiridine. NR2A-containing NMDA receptors and CREB signaling have important functions in the induction of ischemic tolerance. This may provide potential novel therapeutic strategies to treat ischemic stroke.

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Regulation of mitogen‐activated protein kinases by glutamate receptors

Cited by 218 publications

References 106 publications

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

Activation of NR2A Receptors Induces Ischemic Tolerance through CREB Signaling

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