Combined 17β-Oestradiol and Progesterone Treatment Prevents Neuronal Cell Injury in Cortical but not Midbrain Neurones or Neuroblastoma Cells

2009 ◽  
Vol 21 (10) ◽  
pp. 841-849 ◽  
Author(s):  
L. Lorenz ◽  
J. Dang ◽  
M. Misiak ◽  
A. Tameh Abolfazl ◽  
C. Beyer ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Yu-jie Li ◽  
Wei Zhao ◽  
Xu-jiao Yu ◽  
Feng-xian Li ◽  
Zi-ting Liu ◽  
...  

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury.


1983 ◽  
Vol 11 (3) ◽  
pp. 135-145
Author(s):  
Erik Walum

Summary Acrylamide, a well known neurotoxic compound, was used in a first evaluation of cultured mouse neuroblastoma cells as an alternative to animal models for neurotoxicological studies. Hence, the effects of acrylamide on the growth, size, morphology and leucine incorporation of three neuroblastoma (41A3, N18 and N1E115), one neuroblastoma x glioma hybrid (NG108CC15), two glioma (138MG and C6) and two fibroblast (RLF and RMC) cell lines were studied. It was found that the concentration of acrylamide needed to inhibit the growth by 50% in 24 hr was similar in all cell lines, i.e. around 2 x 10-4g/ml culture medium. In the two cell lines, N1E115 and NG108CC15, acrylamide at this concentration caused neurite retraction and at higher concentrations (5 x 10-4g/ml) a decrease in cell viability. In a concentration range of 5 x 10-5 - 5 x 10-4g/ml acrylamide did not affect cell size, or at 2 x 10-4g/ml incorporation of leucine into trichloroacetic acid precipitable material. It is suggested that acrylamide interferes with a biochemical process common to all the tested cells, but of greater importance in differentiated nerve cells than in others. Whether this process is consistent with the in vivo target for the neurotoxic action of acrylamide remains to be unravelled.


Author(s):  
Ruya Çolak ◽  
Aslı Celik ◽  
Gulden Diniz ◽  
Senem Alkan Özdemir ◽  
Osman Yilmaz ◽  
...  

Objective This study aimed to evaluate the efficacy of Pycnogenol (PYC) and its antioxidant and antiapoptotic effect in an experimental hypoxic-ischemic (HI) rat model. Study Design A total of 24 Wistar albino rats who were on the seventh postnatal day were divided into three groups with developed HI brain injury model under the sevoflurane anesthesia: 40 mg/kg PYC was given to Group A, saline was given to Group B, and the sham group was Group C. Neuronal apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemically stained manually with primer antibodies of tumor necrosis factor-α and interleukin-1β. Results The neuronal cell injury was statistically lower in the PYC treatment group. Conclusion This is the first study that investigates the role of PYC in the HI brain injury model. PYC reduces apoptosis and neuronal injury in the cerebral tissue of the rats. PYC may be a protective agent against hypoxic-ischemic encephalopathy. Key Points


2020 ◽  
Vol 117 (28) ◽  
pp. 16516-16526 ◽  
Author(s):  
Ting Tao ◽  
Hui Shi ◽  
Luca Mariani ◽  
Brian J. Abraham ◽  
Adam D. Durbin ◽  
...  

LIN28B is highly expressed in neuroblastoma and promotes tumorigenesis, at least, in part, through inhibition oflet-7microRNA biogenesis. Here, we report that overexpression of either wild-type (WT) LIN28B or a LIN28B mutant that is unable to inhibitlet-7processing increases the penetrance of MYCN-induced neuroblastoma, potentiates the invasion and migration of transformed sympathetic neuroblasts, and drives distant metastases in vivo. Genome-wide chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) and coimmunoprecipitation experiments show that LIN28B binds active gene promoters in neuroblastoma cells through protein–protein interaction with the sequence-specific zinc-finger transcription factor ZNF143 and activates the expression of downstream targets, including transcription factors forming the adrenergic core regulatory circuitry that controls the malignant cell state in neuroblastoma as well asGSK3BandL1CAMthat are involved in neuronal cell adhesion and migration. These findings reveal an unexpectedlet-7–independent function of LIN28B in transcriptional regulation during neuroblastoma pathogenesis.


1998 ◽  
Vol 274 (6) ◽  
pp. G978-G983 ◽  
Author(s):  
Karen E. Hall ◽  
John W. Wiley

Understanding of the pathophysiology of neuronal injury has advanced remarkably in the last decade. This largely reflects the burgeoning application of molecular techniques to neuronal cell biology. Although there is certainly no consensus hypothesis that explains all aspects of neuronal injury, a number of interesting observations have been published. In this brief review, we examine mechanisms that appear to contribute to the pathophysiology of neuronal injury, including altered Ca2+ signaling, activation of the protease cascades coupled to apoptosis, and mitochondrial deenergization associated with release of cytochrome c, production of free radicals, and oxidative injury. Finally, evidence for neuroprotective mechanisms that may ameliorate cell injury and/or death are reviewed. Little information has been published regarding the mechanisms that mediate injury in the enteric nervous system, necessitating a focus on models outside the gastrointestinal (GI) tract, which may provide insights into enteric nervous system injury.


1997 ◽  
Vol 323 (1) ◽  
pp. 245-250 ◽  
Author(s):  
Pasqualina BUONO ◽  
Lisa de CONCILIIS ◽  
Paola IZZO ◽  
Francesco SALVATORE

A DNA region located at around -200 bp in the 5´ flanking region (region D) of the human brain-type fructose-bisphosphate aldolase (aldolase C) gene has been analysed. We show by transient transfection assay and electrophoretic-mobility-shift assay (EMSA) that the binding of transcriptional activators to region D is much more efficient (80% versus 30%) in human neuroblastoma cells (SKNBE) than in the non-neuronal cell line A1251, which contains low levels of aldolase C mRNA. The sequence of region D, CAAGGTCA, is very similar to the AAAGGTCA motif present in the mouse steroid 21-hydroxylase gene; the latter motif binds nerve-growth-factor-induced B factor (NGFI-B), which is a member of the thyroid/steroid/retinoid nuclear receptor gene family. Competition experiments in EMSA and antibody-directed supershift experiments showed that NGFI-B is involved in the binding to region D of the human aldolase C gene. Furthermore, the regulation of the aldolase C gene (which is the second known target of NGFI-B) expression during development parallels that of NGFI-B.


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