Kainic Acid Down-regulates NOP Receptor Density and Gene Expression in Human Neuroblastoma SH-SY5Y Cells

Cannarsa, Rosalia; Landuzzi, Daniela; Cavina, Chiara; Candeletti, Sanzio; Romualdi, Patrizia

doi:10.1007/s12031-008-9038-x

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…Recently, new evidence concerning the existence of a cross-talk between NOP and kainate receptors, leading to interplay between glutamate and N/ OFQ circuits, is also provided. 60 The present results showed that N/OFQ(1-13)NH 2 and its structural analogue [Orn 9 ]N/OFQ(1-13)NH 2 did not change the endogenous levels of antioxidant markers, tested in brain of control animals. Moreover, injected 30 min before KA, the both neuropeptides had no effects on KA-induced changes in all parameters, tested.…”

Section: Discussionsupporting

confidence: 45%

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

Tsvetanova

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Alexandrova

et al. 2009

Cell Biochemistry & Function

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In-vivo effects of nociceptin (N/OFQ(1-13)NH(2)) on the levels of lipid peroxidation and cell enzyme (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzyme (glutathione) antioxidants in brain of control and kainic acid-treated rats were studied. N/OFQ(1-13)NH(2) effects were compared with those of its structural analogue [Orn(9)]N/OFQ(1-13)NH(2). Kainic acid (25 microg, i.c.v) increased the lipid peroxidation (4 and 24 h after kainic acid treatment) and decreased the glutathione level (1 h after kainic acid injection). We failed to find, any changes in antioxidant enzyme activities, independently of the time of kainic acid treatment. At the background of kainic acid-effects, N/OFQ(1-13)NH(2) and [Orn(9)] N/OFQ(1-13)NH(2), injected 30 min before kainic acid, had no effects on all parameters, tested in brain. In addition, the neuropeptides did not change the antioxidant status in brain of control animals. It might be concluded that N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2) have neither pro- nor anti-oxidant activity.

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Section: Discussionsupporting

confidence: 45%

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

Tsvetanova

Павлова

Alexandrova

et al. 2009

Cell Biochemistry & Function

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“…2 b), Western blot analyses were carried out to detect secretion of sPLA 2 -IIA-EGFP fusion protein into the culture media. The dose of AMPA, KA, NMDA or glutamate used in these experiments was 10 M , which is less than the toxic doses of 40 M for AMPA [68] ; 25-200 M for KA [67,69] ; 0.1-5 m M for NMDA [69,70] , and 2-100 m M for glutamate [71,72] for human neuroblastoma SH-SY5Y cells. External application of KA or AMPA resulted in increased exocytosis and release of sPLA 2 -IIA whereas NMDA did not show any significant effect ( fig.…”

Section: Discussionmentioning

confidence: 93%

“…We therefore sought to determine whether sPLA 2 could be released from cells in response to excitatory, glutamatergic stimulation. This was carried out on SH-SY5Y cells, which have been shown to express NMDA, AMPA and KA receptors [65][66][67] including the GluR5 subunit [59] (see online supplementary figure 1, www. karger.com/doi/10.1159/000330414).…”

Section: Discussionmentioning

confidence: 99%

Kainate Receptors Mediate Regulated Exocytosis of Secretory Phospholipase A2 in SH-SY5Y Neuroblastoma Cells

Than

Tan²,

Ong

et al. 2011

Neurosignals

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Secretory phospholipase A₂ (sPLA₂) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA₂ (sPLA₂-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA₂ is itself released, and a possible relation between glutamate receptors and sPLA₂ exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA₂-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA₂-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA₂-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA₂-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA₂-IIA secretion. Moreover, KA-induced sPLA₂-IIA secretion is dependent on Ca²⁺ and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA₂ secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases.

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“…To affect the electrical activity of the cells in culture, SH-SY5Y cells were treated with increasing concentrations of KA. It is known that SH-SY5Y cells express kainate receptors and that the treatment with KA can affect cell viability (Cannarsa, Landuzzi, Cavina, Candeletti, & Romualdi, 2008;Connor, Yeo, & Henderson, 1996).…”

mentioning

confidence: 99%

Functions of extracellular vesicle mediated signaling from blood to brain in neurodegenerative diseases

Kur¹

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Cellular communication is a concept that can be explained as the transfer of signals or material (such as cytokines, ions, small molecules) between cells from the same or different type, across either short or long distances. Once this signal or material is received, it will, as a rule, promote a functional effect. Several routes, involved in this transfer, are well described and are of global importance for organ/tissue communication in an organism. The brain interacts dynamically with the immune system, and the main route known to mediate this communication, is via the release of cytokines (by peripheral blood cells), which can then activate certain brain cell types, such as microglia, directly, or activate the vagus nerve transferring signals to neuronal populations in the brain. The communication between these two systems plays a key role in the pathophysiology of neurodegenerative diseases, and the mechanisms involved in this interaction are of central importance for understanding disease initiation and progression and search for therapeutic models. The Momma lab previously addressed the mechanisms of interaction between the peripheral immune system and the brain by investigating cellular fusion of haematopoietic cells with neurons after inflammation. They addressed the question of whether this phenomenon also occurs under non-invasive conditions. To approach this problem, a genetic tracing model that relies on the Cre-Lox recombination system was used. Transgenic mice expressing Cre recombinase specifically in the haematopoietic lineage were crossed into a Cre-reporter background, thus all haematopoietic cells irreversibly express the reporter marker-gene EYFP. Using this model, EYFP was detected in non-haematopoietic tissues, suggesting the existence of a communication mechanism never described before. As cells containing two nuclei were never detected, fusion as a mechanism was excluded, suggesting that Cre reaches non-haematopoietic cells via a different signalling pathway. The Momma lab investigated whether the transfer of material through extracellular vesicles (EVs) could be behind this periphery-to-brain communication. Using the genetic mouse model, they were able to trace the transfer of Cre RNA via EVs between cells in vivo, generating the first in vivo evidence of functional RNA transfer by EVs between blood and brain. The last decade has witnessed a rapid expansion of the field of EVs. Initially considered as waste disposal material, recent evidence has challenged this view. EVs are currently considered as a widespread intercellular communication system that can transport and transfer all types of biomolecules, from nucleic acids to lipids and proteins. However, several important questions are still under investigation. One of them is whether EVs are involved in brain pathophysiology, as inflammation plays an important role in onset and progression of neurodegenerative diseases and is well described in Parkinson Disease (PD). Based on preliminary data in a mouse, peripherally injected with a low dose of Lipopolysaccharide (LPS, an endotoxin found in the outer-membrane of Gram-negative bacteria, which causes an immune response), neurons and other cell population in the brain take up EVs from the periphery. Particularly, dopaminergic neurons from Substantia Nigra and Ventral Tegmental Area have been shown to receive functional RNA, transported through EVs, which can lead up to 20% of recombination. Furthermore, different neuronal populations from Hippocampus, Cortex and Cerebellum exhibit recombination, indicating a widespread signalling from blood to the brain. Therefore, the goal of my PhD thesis was to investigate the mechanisms of this transfer and the triggers that lead to EV uptake by neural cells in vivo both in pathological and physiological conditions. In this project, the extent and function of EV-mediated signalling from blood to brain is explored in the context of peripheral inflammation and neurodegenerative diseases. Firstly, EVs isolated from WT mice were further characterized using size-exclusion chromatography (SEC), Western Blot (WB) and electron microscopy in order to extend the knowledge from previous work done in the Momma lab. Secondly, to expand on the biological relevance of the fact that inflammation is correlated with an increase in EV uptake, different approaches using the genetic murine tracing model were used. Recombination events from haematopoietic cells to the brain have been followed after peripheral injection of LPS. Peripheral inflammation caused by LPS injection led to widespread recombination events in the brain, specifically in microglia and neurons, including dopaminergic (DA) neurons. In contrast, astrocytes, oligodendrocytes and endothelial cells were never or very rarely recombined. Additionally, peripheral LPS injection in a murine model, where Cre is expressed only in erythrocytes, led to recombination events only in microglia, suggesting that the type of EV-secreting cell plays a role in the targeting of EVs to a specific cell population.

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Kainic Acid Down-regulates NOP Receptor Density and Gene Expression in Human Neuroblastoma SH-SY5Y Cells

Cited by 7 publications

References 30 publications

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

Kainate Receptors Mediate Regulated Exocytosis of Secretory Phospholipase A2 in SH-SY5Y Neuroblastoma Cells

Functions of extracellular vesicle mediated signaling from blood to brain in neurodegenerative diseases

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Kainic Acid Down-regulates NOP Receptor Density and Gene Expression in Human Neuroblastoma SH-SY5Y Cells

Cited by 7 publications

References 30 publications

Are nociceptin(1‐13)NH2and its structural analogue [ORN9]nociceptin(1‐13)NH2able to affect brain antioxidant status in control and kainic acid‐treated rats?

Are nociceptin(1‐13)NH2and its structural analogue [ORN9]nociceptin(1‐13)NH2able to affect brain antioxidant status in control and kainic acid‐treated rats?

Kainate Receptors Mediate Regulated Exocytosis of Secretory Phospholipase A2 in SH-SY5Y Neuroblastoma Cells

Functions of extracellular vesicle mediated signaling from blood to brain in neurodegenerative diseases

Contact Info

Product

Resources

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Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?