Insulin Blocks Glutamate-Induced Neurotoxicity in Differentiated SH-SY5Y Neuronal Cells

Nampoothiri, Madhavan; Reddy, Neetinkumar D.; John, Jessy; Kumar, Nitesh; Nampurath, Gopalan Kutty; Chamallamudi, Mallikarjuna Rao

doi:10.1155/2014/674164

Cited by 41 publications

(39 citation statements)

References 44 publications

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“…Decreased cell viability was associated with increased intracellular calcium concentration and enhanced A B apoptosis, as well as necrosis. Consistent with the findings of the present study, a recent study demonstrated that treatment with 20 mM glutamate induced apoptosis and elevated reactive oxygen species (ROS) generation in SH-SY5Y cells (13). RIP kinase 1 and RIP kinase 3 are key signaling molecules in programmed necrosis (9,10).…”

Section: Discussionsupporting

confidence: 90%

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

Sun

Shi

et al. 2016

Molecular Medicine Reports

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Abstract. The aim of the present study was to elucidate the intracellular mechanisms that cause neuronal cell death following exposure to excitatory neurotransmitter-induced neurotoxicity, neurotoxins and oxidative stress. Human SH-SY5Y neuroblastoma cells were exposed to various stimuli, including glutamate, 6-hydroxydopamine (6-OHDA), and glucose oxidase, and cell viability was determined by MTT assay. Early apoptosis and necrosis were examined by Annexin V/propidium iodide double staining and flow cytometric analysis. Intracellular calcium ion concentration and mitochondrial membrane potential were assessed by Fluo-3a and JC-1 staining, respectively. In addition, protein expression of receptor-interacting protein (RIP) kinase 1 and RIP kinase 3 were evaluated by western blotting. Glutamate, 6-OHDA and glucose oxidase treatment decreased cell viability. Glutamate induced apoptosis and necrosis, whereas, 6-OHDA induced cell necrosis and glucose oxidase induced apoptosis. Furthermore, glutamate, 6-OHDA or glucose oxidase treatment significantly increased intracellular calcium concentrations (P<0.05). The effect of glutamate on mitochondrial membrane potential varied with high and low concentrations, whereas 6-OHDA and glucose oxidase significantly increased the mitochondrial membrane potential in the SH-SY5Y cells (P<0.05). Glutamate significantly upregulated expression levels of RIP kinase 1 (P<0.05), but not RIP kinase 3. These findings demonstrate that the response of SH-SY5Y cells varies with the stimuli. Furthermore, RIP kinase 1 may specifically regulate programmed necrosis in glutamate-mediated excitatory toxicity, but not in cell damage induced by either 6-OHDA or glucose oxidase.

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Section: Discussionsupporting

confidence: 90%

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

Sun

Shi

et al. 2016

Molecular Medicine Reports

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“…Neuroprotective effects were assayed in SH-SY5Y cells injured by glutamate as reported previously [22]. SH-SY5Y cells were obtained from Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College.…”

Section: Neuroprotective Effects Assaymentioning

confidence: 99%

Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix

Gong

Zhou

et al. 2016

Molecules

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Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4) showed cytotoxicity against three cancer cell lines, with IC 50 values of 13.82, 6.79, and 7.92 µM, respectively. Tokinolide A (6) and tokinolide C (6) exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4). We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1), Z-butylidenephthalide (3) and tokinolide A (6) exhibited significant neuroprotective effects.

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“…Insulin therapies are being tested as a potential treatment in several neurodegenerative disorders based on the following observations: (1) insulin dysfunction in several CNS diseases (Table 1); (2) the observed potential of insulin to alleviate cytotoxic insult to neuronal cells in culture [40] ; (3) its ability to enhance learning and memory in rodents [41,42] . For example, the administration of intranasal insulin has already shown promising effects in humans by halting further memory loss in mild cognitive impairment and Alzheimer's disease [43,44] .…”

Section: Major Depressive Disordermentioning

confidence: 99%

The Role of Insulin and Incretins in Neuroinflammation and Neurodegeneration

2015

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Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) are incretin hormones secreted from intestinal cells in response to incoming nutrients. The release of these incretins triggers the production and secretion of insulin from pancreatic β cells, which upregulates the transport of glucose from the blood stream into the muscles, liver and adipose tissue for storage; therefore, insulin and incretins are vital to maintaining energy homeostasis within the body. Recently, it has been recognized that the activity of these hormones is not limited to the periphery, but extends to the central nervous system (CNS) as well. Within the CNS, insulin and incretins function as components of the anti-apoptotic and growth-regulating signaling cascades. Moreover, anti-inflammatory and neuroprotective roles for these hormones in the CNS have also been demonstrated. Specific discoveries have been made suggesting that insulin, GLP-1 and GIP may inhibit pathological processes in several CNS diseases, such as Alzheimer's disease, Parkinson's disease, and schizophrenia.

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Insulin Blocks Glutamate-Induced Neurotoxicity in Differentiated SH-SY5Y Neuronal Cells

Cited by 41 publications

References 44 publications

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix

The Role of Insulin and Incretins in Neuroinflammation and Neurodegeneration

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