Neuronal differentiation is accompanied by NSP-C expression

Hens, J. Martínez; Nuydens, Ronny; Geerts, Hugo; Senden, Nicole H. M.; Ven, Wim J.M. Van de; Roebroek, Anton; Velde, H. J. K. Van De; Ramaekers, Frans C. S.; Broers, J. L. V.

doi:10.1007/s004410051054

Cited by 36 publications

(32 citation statements)

References 15 publications

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“…[23][24][25] RTN-1C represents the smallest variant of the reticulon 1 gene 26 and it is specifically expressed by neurons and cells of neuroendocrine tissue. 27 In our study, we used the previously developed tetracycline-inducible SH-SY5Y RTN-1C human neuroblastoma model 23 consisting of a SH-SY5Y cell line stably expressing tetracycline-inducible RTN-1C (SH-SY5Y RTN-1C ) and a control cell line expressing the regulator vector alone (SH-SY5Y Tet12 ) (Figure 1a). After addition of doxycycline, a tetracycline derivative, SH-SY5Y RTN-1C cells overexpress RTN-1C within hours, reaching a peak around 6 h that remains constant for several days (Figure 1b).…”

Section: Resultsmentioning

confidence: 99%

Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin

et al. 2007

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Some chemotherapeutic agents can elicit apoptotic cancer cell death, thereby activating an anticancer immune response that influences therapeutic outcome. We previously reported that anthracyclins are particularly efficient in inducing immunogenic cell death, correlating with the pre-apoptotic exposure of calreticulin (CRT) on the plasma membrane surface of anthracyclintreated tumor cells. Here, we investigated the role of cellular Ca 2 þ homeostasis on CRT exposure. A neuroblastoma cell line (SH-SY5Y) failed to expose CRT in response to anthracyclin treatment. This defect in CRT exposure could be overcome by the overexpression of Reticulon-1C, a manipulation that led to a decrease in the Ca 2 þ concentration within the endoplasmic reticulum lumen. The combination of Reticulon-1C expression and anthracyclin treatment yielded more pronounced endoplasmic reticulum Ca 2 þ depletion than either of the two manipulations alone. Chelation of intracellular (and endoplasmic reticulum) Ca 2 þ , targeted expression of the ligand-binding domain of the IP 3 receptor and inhibition of the sarco-endoplasmic reticulum Ca 2 þ -ATPase pump reduced endoplasmic reticulum Ca 2 þ load and promoted pre-apoptotic CRT exposure on the cell surface, in SH-SY5Y and HeLa cells. These results provide evidence that endoplasmic reticulum Ca 2 þ levels control the exposure of CRT. In contrast to prior belief, apoptotic cell death can be immunogenic and hence elicits an active immune response against dying tumor cells. 1 This is therapeutically relevant because immune defects that compromise the response against apoptotic cells reduce the efficacy of anticancer chemotherapy, both in suitable animal models and in patients. 2 We found that anthracyclins and g-irradiation are particularly efficient in inducing immunogenic cell death, at least in mouse models. [3][4][5] The immunogenicity of cellular demise correlates with the exposure of calreticulin (CRT) on the plasma membrane (PM) surface of stressed tumor cells, a phenomenon that manifests before the cells acquire signs of apoptosis such as phosphatidylserine exposure. Inhibition of CRT exposure curtails the capacity of anthracyclin-treated or irradiated tumor cells to vaccinate against cancer and reduces the therapeutic efficacy of anthracyclins on tumors established in immunocompetent hosts. 3-5 Provision of recombinant CRT or drug-mediated enforcement of CRT exposure rendered per se nonimmunogenic chemotherapies (for instance with etoposide and mitomycin C) immunogenic and boosted their therapeutic efficacy. 5 These results suggest that CRT exposure is both necessary and sufficient to render conventional chemotherapies immunogenic.CRT is an abundant Ca 2 þ -binding chaperone that is mostly present in the endoplasmic reticulum (ER) lumen, although it can also be found in other subcellular localizations. 6,7 When present on the surface of damaged cells, it can serve as an 'eat-me' signal and hence facilitate the recognition and later engulfment of the dying cells by macrophages 8 or by dendrit...

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Section: Resultsmentioning

confidence: 99%

Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin

et al. 2007

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“…Hens and coworkers (40) recently showed that highly differentiated neuronal cell lines expressed NSP-C to a higher extent than cell lines showing less neuronal differentiation. Moreover, induction of neuronal differentiation in undifferentiated pheochromocytoma PC12 cells induced a strong increase in NSP-C expression.…”

Section: Discussionmentioning

confidence: 99%

Neurodegeneration, Neuronal Loss, and Neurotransmitter Changes in the Adult Guinea Pig with Perinatal Asphyxia

et al. 2003

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There is only limited morphologic information on long-term alterations and neurotransmitter changes after perinatal asphyxia, and no long-term study showing neurodegeneration has been reported so far. We used an animal model for perinatal asphyxia well documented in the rat to investigate the guinea pig as a species highly mature at birth. Cesarean section was performed on full-term pregnant guinea pigs, and pups, still in membranes, were placed into a water bath at 37°C for asphyxia periods from 2 to 4 min. Thereafter pups were given to surrogate mothers and examined at 3 mo of age. We studied brain areas reported to be hypoxia-sensitive. Neurodegeneration was evaluated by fluorojade, neuronal loss by Nissl, reactive gliosis by glial fibrillary acidic protein staining, and differentiation by neuroendocrinespecific protein C immunoreactivity. We tested tyrosine hydroxylase, the vesicular monoamine transporter, and dopamine ␤-hydroxylase, representing the monoaminergic system; the vesicular acetylcholine transporter; and the excitatory amino acid carrier 1. Neurodegeneration was evident in cerebellum, hippocampal area CA1, and hypothalamus, and neuronal loss could be observed in cerebellum and hypothalamus; gliosis was observed in cerebellum, hippocampus, hypothalamus, and parietal cortex; dedifferentiation was found in hypothalamus and striatum; and monoaminergic, cholinergic, and amino acidergic deficits were shown in several brain regions. The major finding of the present study was that neurodegeneration and dedifferentiation evolved in the guinea pig, a species highly mature at birth. The relevance of this contribution is that a simple animal model of perinatal asphyxia resembling the clinical situation of intrauterine hypoxia-ischemia and presenting with neurodegeneration was characterized. PA continues to be a major cause of neurologic injury in the newborn, leading to reversible and irreversible brain damage ranging from minimal brain dysfunction to death (1-3). After a hypoxic-ischemic insult certain neuron subpopulations are known to die whereas others survive (4 -6). This phenomenon, referred to as selective vulnerability, occurs in adult and neonatal brain. Neurons in the hippocampus, cerebellum, striatum, thalamus, and neocortex have been identified to be vulnerable to hypoxic-ischemic insults.Apart from acute cell death the question arises whether PA can provoke detrimental effects on the CNS later in life, e.g. as induction of neurodegeneration. There are no long-term studies available reporting on neurodegeneration after PA, and therefore we included a marker for the detection of degenerating cells. Because only subtle morphologic differences between normal and degenerating cells may exist and thus degenerating neurons could be missed easily, we performed FJ staining as the staining pattern of this dye corresponds to the pattern of argyrophilia, staining cell bodies, dendrites, and axon terminals of degenerating neurons but not healthy neurons, myelin, vascular elements, or neuropil (7).In addition...

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“…Also known as neural cell adhesion molecule (NCAM) [31] Oct-4 Expressed by undifferentiated embryonic stem cells and embryonic germ cells [32] Nestin Stem/progenitor cells, glioma cells, and tumor endothelial cells in the mammalian CNS [33] Class III β-tubulin Also referred to as TuJ1. Expressed in central and peripheral nervous systems (CNS and PNS) where it is prominently expressed during fetal and postnatal development.…”

Section: Cd56mentioning

confidence: 99%

Trophic factor induction of human umbilical cord blood cellsin vitroandin vivo

et al. 2007

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The mononuclear fraction of human umbilical cord blood (HUCBmnf) is a mixed cell population that multiple research groups have shown contains cells that can express neural proteins. In these studies, we have examined the ability of the HUCBmnf to express neural antigens after in vitro exposure to defined media supplemented with a cocktail of growth and neurotrophic factors. It is our hypothesis that by treating the HUCBmnf with these developmentally-relevant factors, we can expand the population, enhance the expression of neural antigens and increase cell survival upon transplantation. Prior to growth factor treatment in culture, expression of stem cell antigens is greater in the non-adherent HUCBmnf cells compared to the adherent cells (p < 0.05). Furthermore, treatment of the non-adherent cells with growth factors, increases BrdU incorporation, especially after 14 days in vitro (DIV). In HUCBmnf-embryonic mouse striata co-culture, a small number of growth factor treated HUCBmnf cells were able to integrate into the growing neural network and express immature (nestin and TuJ1) and mature (GFAP and MAP2) neural markers. Treated HUCBmnf cells implanted in the subventricular zone predominantly expressed GFAP although some grafted HUCBmnf cells were MAP2 positive. While short-term treatment of HUCBmnf cells with growth and neurotrophic factors enhanced proliferative capacity in vitro and survival of the cells in vivo, the treatment regimen employed was not enough to ensure long-term survival of HUCBmnf-derived neurons necessary for cell replacement therapies for neurodegenerative diseases.

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Neuronal differentiation is accompanied by NSP-C expression

Cited by 36 publications

References 15 publications

Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin

Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin

Neurodegeneration, Neuronal Loss, and Neurotransmitter Changes in the Adult Guinea Pig with Perinatal Asphyxia

Trophic factor induction of human umbilical cord blood cellsin vitroandin vivo

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