Role of N-Methyl-d-aspartate Receptors in the Neuroprotective Activation of Extracellular Signal-regulated Kinase 1/2 by Cisplatin

Gozdz, Agata; Habas, Agata; Jaworski, Jacek; Zielińska, Magdalena; Chlystun, Marcin; Jalili, Ahmad; Hetman, Michał

doi:10.1074/jbc.m301554200

Cited by 38 publications

(58 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caspase-3 activity was determined using a colorimetric assay (Promega) as described previously (Gozdz et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

“…We previously demonstrated that in cortical neurons, which were treated with DNA-damaging drugs including CPT, BDNF suppresses apoptosis by activating the ERK1/2 pathway (Hetman et al, 1999;Gozdz et al, 2003). Others have shown that ERK1/2 mediates BDNF protection against TD (Bonni et al, 1999).…”

Section: Ksr1 Contributes To Antiapoptotic Effects Of Bdnfmentioning

confidence: 99%

“…ERK1/2 activation by NGF or BDNF suppresses DNA damage-induced apoptosis in sympathetic or cortical neurons, respectively (Anderson and Tolkovsky, 1999;Hetman et al, 1999;Gozdz et al, 2003). Also, in cerebellar granule neurons, ERK1/2 activation by either BDNF or cAMP elevation reduces trophic deprivation (TD)-induced apoptosis (Villalba and Journot, 1997;Bonni et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of Kinase Suppressor of Ras-1 in Neuronal Survival Signaling by Extracellular Signal-Regulated Kinase 1/2

Szatmári¹,

Kalita²,

Kharebava³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Scaffolding proteins including kinase suppressor of Ras-1 (KSR1) determine specificity of signaling by extracellular signal-regulated kinase 1/2 (ERK1/2), enabling it to couple diverse extracellular stimuli to various cellular responses. The scaffolding protein(s) that contributes to ERK1/2-mediated neuronal survival has not yet been identified. In cultured rat cortical neurons, BDNF activates ERK1/2 to enhance neuronal survival by suppressing DNA damage-or trophic deprivation-induced apoptosis. Here we report that in this system, BDNF increased KSR1 association with activated ERK1/2, whereas KSR1 knockdown with a short hairpin (sh) RNA reduced BDNFmediated activation of ERK1/2 and protection against a DNA-damaging drug, camptothecin (CPT). In contrast, BDNF suppression of trophic deprivation-induced apoptosis was unaffected by shKSR1 although blocked by shERK1/2. Also, overexpression of KSR1 enhanced BDNF protection against CPT. Therefore, KSR1 is specifically involved in antigenotoxic activation of ERK1/2 by BDNF. To test whether KSR1 contributes to ERK1/2 activation by other neuroprotective stimuli, we used a cAMP-elevating drug, forskolin. In cortical neurons, ERK1/2 activation by forskolin was protein kinase A (PKA) dependent but TrkB (receptor tyrosine kinase B) independent and was accompanied by the increased association between KSR1 and active ERK1/2. Forskolin suppressed CPT-induced apoptosis in a KSR1 and ERK1/2-dependent manner. Inhibition of PKA abolished forskolin protection, whereas selective PKA activation resulted in an ERK1/2-and KSR1-mediated decrease in apoptosis. Hence, KSR1 is critical for the antiapoptotic activation of ERK1/2 by BDNF or cAMP/PKA signaling. In addition, these novel data indicate that stimulation of cAMP signaling is a candidate neuroprotective strategy to intervene against neurotoxicity of DNA-damaging agents.

show abstract

“…Caspase-3 activity was determined using a colorimetric assay (Promega) as described previously (Gozdz et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

Section: Ksr1 Contributes To Antiapoptotic Effects Of Bdnfmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Kinase Suppressor of Ras-1 in Neuronal Survival Signaling by Extracellular Signal-Regulated Kinase 1/2

Szatmári¹,

Kalita²,

Kharebava³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…As anticancer DNA-damaging cisplatin induces a prolonged activation of ERK1/2, whose outcomes on cell death/cell survival are cell-type dependent (Gozdz et al, 2003;Arany et al, 2004), we monitored ERK phosphorylation by western blot analysis during dose-response treatment of cisplatin on U87MG-expressing sense-and antisense-DUSP6 (Figure 4c). Immunoblot analysis showed that forced expression of DUSP6 was sufficient to inhibit phosphorylation of ERK, and increasing doses of cisplatin were not able to change it at all (as reported in U87MG DUSP6-infected cells).…”

Section: Dusp6 Regulation and Function In Glioblastoma Cancer Cells Smentioning

confidence: 99%

Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas

Messina

Frati

Leonetti³

et al. 2011

Oncogene

View full text Add to dashboard Cite

Dual-specificity phosphatase 6 (DUSP6, mitogen-activated protein kinase (MAPK) phosphatase 3 or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on extracellular signal-regulated kinase (ERK1/ 2; MAPK1/2) to inactivate the ERK1/2 kinase. DUSP6 is a critical regulator of the ERK signaling cascade and has been implicated as a tumor suppressor. We report here experimental evidences that DUSP6 is transcriptionally upregulated in primary and long-term cultures of human glioblastoma, as assayed by northern hybridization and real-time quantitative PCR, producing constitutive high level of protein expression. Functional assays were performed with adenovirus-mediated expression of DUSP6 in glioblastoma cultures. Protein overexpression inhibits growth by inducing G1-phase delay and increased mitogenic/anchorage dependence and clonogenic potential in vitro. Changes in cell morphology were associated with an increased tumor growth in vivo. Chemoresistance is a major cause of treatment failure and poor outcome in human glioblastomas. Importantly, DUSP6 overexpression increased resistance to cisplatinmediated cell death in vitro and in vivo. Antisense-mediated depletion of DUSP6 acted in lowering the threshold to anticancer DNA-damaging drugs. We conclude that upregulation of DUSP6 exerts a tumor-promoting role in human glioblastomas exacerbating the malignant phenotype.

show abstract

“…For example, by suppressing the activation of glycogen synthase kinase-3␤, low levels of NMDA receptor agonist protect cortical neurons from apoptosis because of phosphatidylinositol-3-kinase blockade (57). Treatment of cortical neurons with cisplatin, a neurotoxic antimitotic, triggers neuroprotective mechanisms by enhancing NMDA receptor activity and thus increasing ERK1͞2 signaling (58). Similarly, it has been demonstrated both in vivo and in cell culture that small ischemic events can trigger a NMDA receptordependent response that provides protection from subsequent larger ischemic events (59,60).…”

Section: Nmda Receptor-dependent Protection From Exogenous Challengementioning

confidence: 99%

NMDA receptors promote survival in somatosensory relay nuclei by inhibiting Bax-dependent developmental cell death

Vaccari

Casey

Aleem

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Naturally occurring cell death is a universal feature of developing nervous systems that plays an essential role in determining adult brain function. Yet little is known about the decisions that select a subset of CNS neurons for survival and cause others to die. We report that postnatal day 0 NMDA receptor subunit 1 (NMDAR1) knockout mice display an Ϸ2-fold increase in cell death in the brainstem trigeminal complex (BSTC), including all four nuclei that receive somatosensory inputs from the face (principalis, oralis, interpolaris, and caudalis). Treatment with the NMDA receptor antagonist dizocilpine maleate (MK-801) for 24 h before birth also caused an increase in cell death that reached statistical significance in two of the four nuclei (oralis and interpolaris). The neonatal sensitivity to NMDA receptor hypofunction in the BSTC, and in its main thalamic target, the ventrobasal nucleus (VB), coincides with the peak of naturally occurring cell death and trigeminothalamic synaptogenesis. At embryonic day 17.5, before the onset of these events, NMDAR1 knockout does not affect cell survival in either the BSTC or the VB. Immunostaining for active caspase-3 and the neuronal marker Hu specifically confirms the presence of dying neurons in the BSTC and the VB of NMDAR1 knockout neonates. Finally, genetic deletion of Bax rescues these structures from the requirement for NMDA receptors to limit naturally occurring cell death. Taken together, the results indicate that NMDA receptors play a survival role for somatosensory relay neurons during synaptogenesis by inhibiting Bax-dependent developmental cell death.brainstem ͉ neuroprotection ͉ sensory systems ͉ trophic ͉ ventrobasal N eurons in the peripheral nervous system avoid developmental cell death by successfully competing for a limiting supply of neurotrophins from synaptic target tissues (1). The situation in the developing CNS is less clear, where the survival-promoting action of neurotrophins on central neurons is complemented, facilitated, or replaced by other forms of support (2). A strong candidate for this role is the electrical activity that is present in developing neurons and neural circuits (3-5). Most neurons, including those in the somatosensory relay nuclei, express NMDA receptors before or just after exiting the cell cycle, well before synapses are established (6-10). Eliminating NMDA receptor function dramatically increases neuronal cell death during development (11-17), and NMDA receptor hypofunction has been proposed to play a causal role in fetal alcohol syndrome and schizophrenia (18,19). However, the biological significance and the molecular mechanisms of NMDA receptor-regulated neuronal survival in the intact brain remain largely unknown.NMDA receptors are best known for their role in synaptic plasticity. In the adult brain many forms of long-term potentiation and long-term depression require NMDA receptor function (20). During development, the refinement and plasticity of nascent synapses have also been shown to be dependent on NMDA receptors (2...

show abstract

Role of N-Methyl-d-aspartate Receptors in the Neuroprotective Activation of Extracellular Signal-regulated Kinase 1/2 by Cisplatin

Cited by 38 publications

References 41 publications

Role of Kinase Suppressor of Ras-1 in Neuronal Survival Signaling by Extracellular Signal-Regulated Kinase 1/2

Role of Kinase Suppressor of Ras-1 in Neuronal Survival Signaling by Extracellular Signal-Regulated Kinase 1/2

Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas

NMDA receptors promote survival in somatosensory relay nuclei by inhibiting Bax-dependent developmental cell death

Contact Info

Product

Resources

About