scholarly journals Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xia Zhao ◽  
Chao Han ◽  
Zhiwen Zeng ◽  
Linlin Liu ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Cortical Neurons ◽  
Inhibitory Effect ◽  
Phosphorylation Sites ◽  
Tyrosine Residues ◽  
Cultured Cortical Neurons ◽  
Survival Signaling ◽  
Neurotrophic Factor Signaling ◽  
Nmdar Subunits

Glutamate-induced neurotoxicity is involved in various neuronal diseases, such as Alzheimer’s disease. We have previously reported that glutamate attenuated the survival signaling of insulin-like growth factor-1 (IGF-1) by N-methyl-D-aspartate receptors (NMDARs) in cultured cortical neurons, which is viewed as a novel mechanism of glutamate-induced neurotoxicity. However, the phosphorylation sites of IGF-1 receptor (IGF-1R) affected by glutamate remain to be elucidated, and importantly, which subtype of NMDARs plays a major role in attenuating the prosurvival effect of IGF-1 is still unknown. In the present study, glutamate was found to attenuate the tyrosine phosphorylation of the IGF-1R and the prosurvival effect of IGF-1 in primary cultured cortical neurons. NMDAR inhibitors, MK801 and AP-5, blocked the inhibitory effect of glutamate on the phosphorylation of IGF-1R and increased cell survival, while DNQX, LY341495, and CPCCOEt had no effect. Interestingly, we found that glutamate decreased the phosphorylation of tyrosine residues 1131, 1135/1136, 1250/1251, and 1316, while it had no effect on tyrosine 950 in cortical neurons. Moreover, using specific antagonists and siRNA to downregulate individual NMDAR subunits, we found that the activation of NR2B-containing NMDARs was essential for glutamate to inhibit IGF-1 signaling. These findings indicate that the glutamate-induced attenuation of IGF-1 signaling is mediated by NR2B-containing NMDARs. Our study also proposes a novel mechanism of altering neurotrophic factor signaling by the activation of NMDARs.

scholarly journals Protection by nerve growth factor against glutamate-induced cytoxicity in cultured cortical neurons.

1994 ◽  
Vol 64 ◽  
pp. 235
Author(s):  
Shun Shimohama ◽  
Yutaka Tamura ◽  
Akinori Akaike ◽  
Tetsuys Tsukahara ◽  
Jun Kimura
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cortical Neurons ◽  
Nerve Growth ◽  
Cultured Cortical Neurons

Cyclophosphamide promotes cell survival via activation of intracellular signaling in cultured cortical neurons

2010 ◽  
Vol 470 (2) ◽  
pp. 139-144 ◽  
Author(s):  
Hiromi Kitazawa ◽  
Tadahiro Numakawa ◽  
Naoki Adachi ◽  
Emi Kumamaru ◽  
Tuerhong Tuerxun ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cortical Neurons ◽  
Intracellular Signaling ◽  
Cultured Cortical Neurons

Identification of Tyrosine Residues of Importance for Survival Signaling through the Scaffolding Protein Gab2 in Both Wild-Type FLT3 and the FLT3-ITD.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1622-1622
Author(s):  
Kristina Masson ◽  
Tao Liu ◽  
Jianmin Sun ◽  
Lars Ronnstrand
Keyword(s):  
Scaffolding Protein ◽  
Phosphorylation Sites ◽  
Wild Type ◽  
Internal Tandem Duplication ◽  
Tyrosine Residues ◽  
Downstream Signaling ◽  
Juxtamembrane Region ◽  
Future Potential ◽  
Survival Signaling

Abstract The receptor tyrosine kinase FLT3 is normally expressed in hematopoietic progenitor cells and has been implicated as a major cause of transformation in acute myeloid leukemia, where it in approximately 30% of cases is mutated and constitutively active. This is in most cases due to duplication of a DNA sequence coding for amino acids in the juxtamembrane region of FLT3, commonly referred to as ITD (Internal Tandem Duplication). In this study we have identified several novel in vivo tyrosine phosphorylation sites that are phosphorylated in wild-type FLT3 upon ligand stimulation and that are constitutively phosphorylated in the FLT3-ITD. We were able to demonstrate that these phosphorylation sites are critical for full phosphorylation of the scaffolding protein Gab2 both in wild-type FLT3 and FLT3-ITD. Y-to-F mutants of either wild-type FLT3 or FLT3-ITD, lacking these tyrosine residues, fail to phosphorylate Gab2 and demonstrate a considerable reduction in phosphorylation of Akt and Erk. Furthermore, FL-dependent survival and proliferation of wild-type FLT3 expressing Ba/F3 cells as well as FL-independent survival and proliferation of Ba/F3 cells transfected with FLT3-ITD was dramatically reduced by mutation of these tyrosine residues. In the case of the FLT3-ITD, this was shown to correlate with strongly reduced STAT5 phosphorylation. To verify the importance of Gab2 in FLT3-ITD signaling, we used siRNA technology to knock down the expression of Gab2 in the human AML cell line MV4-11 that is known to express FLT3-ITD. Knockdown of Gab2 expression led to a dramatic reduction in the phosphorylation of Akt, Erk and Stat5. To summarize, we have identified novel phosphorylation sites in FLT3 and how they link to downstream signaling of survival and proliferation. These findings not only reveal novel phosphorylation sites in FLT3 but also contribute to the understanding of the molecular mechanism by which FLT3-ITD functions in pathological conditions. Future studies are aiming at elucidating the mechanism by which Gab2 mediates phosphorylation and activation of STAT5, which could be a future potential target for therapy in AML with FLT3-ITD.

Protective effect of nerve growth factor against glutamate-induced neurotoxicity in cultured cortical neurons

1993 ◽  
Vol 632 (1-2) ◽  
pp. 296-302 ◽  
Author(s):  
Shun Shimohama ◽  
Nobuo Ogawa ◽  
Yutaka Tamura ◽  
Akinori Akaike ◽  
Tetsuya Tsukahara ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Protective Effect ◽  
Cortical Neurons ◽  
Nerve Growth ◽  
Cultured Cortical Neurons

scholarly journals Transforming Growth Factor-β1—Modulated Cerebral Gene Expression

2002 ◽  
Vol 22 (9) ◽  
pp. 1114-1123 ◽  
Author(s):  
Sylvain Lesné ◽  
Sophie Blanchet ◽  
Fabian Docagne ◽  
Géraldine Liot ◽  
Laurent Plawinski ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cortical Neurons ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Wild Type ◽  
Chain Reactions ◽  
Polymerase Chain Reactions ◽  
Cultured Cortical Neurons ◽  
The Central Nervous System ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1) plays a central role in the response of the brain to different types of injury. Increased TGF-β1 has been found in the central nervous system of patients with acute or chronic disorders such as stroke or Alzheimer disease. To further define the molecular targets of TGF-β1 in cerebral tissues, a selection of high-density cDNA arrays was used to characterize the mRNA expression profile of 7,000 genes in transgenic mice overexpressing TGF-β1 from astrocytes as compared with the wild-type line. Selected findings were further evaluated by reverse transcription-polymerase chain reactions from independent transgenic and wild-type mice. Furthermore, the expression pattern of seven selected genes such as Delta-1, CRADD, PRSC-1, PAI-1, Apo-1/Fas, CTS-B, and TβR-II were confirmed in either cultured cortical neurons or astrocytes following TGF-β1 treatment. The authors' observations enlarge the repertoire of known TGF-β1–modulated genes and their possible involvement in neurodegenerative processes.

scholarly journals Protective effects of nerve growth factor (NGF) against NOInduced neurotoxicity in cultured cortical neurons.

1996 ◽  
Vol 71 ◽  
pp. 192
Author(s):  
Toshiaki Kume ◽  
Hanae Kouchiyama ◽  
Saioshi Kaneke ◽  
Takehiko Maeda ◽  
Shuji Kaneko ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cortical Neurons ◽  
Protective Effects ◽  
Nerve Growth ◽  
Cultured Cortical Neurons

scholarly journals Basic Fibroblast Growth Factor Evokes a Rapid Glutamate Release through Activation of the MAPK Pathway in Cultured Cortical Neurons*

2002 ◽  
Vol 277 (32) ◽  
pp. 28861-28869 ◽  
Author(s):  
Tadahiro Numakawa ◽  
Daisaku Yokomaku ◽  
Kazuyuki Kiyosue ◽  
Naoki Adachi ◽  
Tomoya Matsumoto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Cortical Neurons ◽  
Mapk Pathway ◽  
Glutamate Release ◽  
Fibroblast Growth ◽  
Cultured Cortical Neurons

Abstract WMP35: Low Level Laser Therapy (LLLT) Protects Against Oxygen-Glucose Deprivation-Induced Neuron Death by Modulating Nitric Oxide and ROS Production In Vitro

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Zhanyang Yu ◽  
Ning Liu ◽  
Yadan Li ◽  
Jianhua Zhao ◽  
Eng H Lo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Cell Survival ◽  
Cortical Neurons ◽  
Post Treatment ◽  
Low Level Laser Therapy ◽  
Primary Neurons ◽  
Ros Production ◽  
Primary Mouse ◽  
Survival Signaling

Background: LLLT has been shown to be neurorprotective against cerebral ischemia in animals. Initial human clinical trials demonstrated safety and potential beneficial profiles. A pivotal clinical trial with TLT is ongoing for ischemic stroke. However, the underlying neuroprotective mechanisms require further definition. We previously showed LLLT protected primary neurons against OGD. In the current study, we tested the hypothesis that LLLT may attenuate OGD-induced nitric oxide (NO) and ROS production and associated cell survival signaling, causing reduced cell death in primary mouse cortical neurons. Method: At day 8 of culture, neurons were subjected to 4 hr OGD. LLLT was applied at 2 hr reoxygenation. NO level, nNOS expression, ROS level, and cell survival signaling were measured post-LLLT. Cell death was measured at 20 hr after OGD. Results were expressed as fold of normal control, mean ± SEM, n = 3-5 per group, P <0.05 was considered statistically significant. Results: OGD significantly increased NO level in primary neurons (2.12 ± 0.47, 2.67 ± 1.07, and 2 ± 0.77 at 5 min, 30 min and 1 hr post-treatment, respectively), but the increase was significantly reduced by LLLT (1.08 ± 0.44 at 5 min and 1.45 ± 0.73 at 30 min post-LLLT). OGD also significantly increased nNOS mRNA level (2.17 ± 0.42, 3.99 ± 1.7, and 2.60 ± 0.7 at 5 min, 30 min and 1 hr post-treatment, respectively), while the increase was significantly ameliorated by LLLT (0.50 ± 0.08 at 30 min and 0.34 ± 0.45 at 1 hr post-LLLT). Additionally, 50 uM NO donor SNAP exposure for 48 hr induced 23.6 ± 2.5% cell death, which was significantly ameliorated by LLLT (12.3 ± 4.2% cell death), indicating LLLT may directly protect NO-mediated neurotoxicity. Furthermore, LLLT significantly reduced OGD-induced ROS production at 5 min, 30 min and 1 hr post-LLLT. Finally, OGD suppressed neuron survival signaling p-Akt and Bcl-2 protein expressions, but they were significantly rescued by LLLT. Conclusion: These results suggest LLLT protection against OGD may be partially through reducing OGD-induced NO and ROS production, and restoring OGD-suppressed cell survival signaling.

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