scholarly journals Cylindromatosis mediates neuronal cell death in vitro and in vivo

2018 ◽  
Vol 25 (8) ◽  
pp. 1394-1407 ◽  
Author(s):  
Goutham K. Ganjam ◽  
Nicole Angela Terpolilli ◽  
Sebastian Diemert ◽  
Ina Eisenbach ◽  
Lena Hoffmann ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell

Selective Release of Calpain Produced αII-Spectrin (α-Fodrin) Breakdown Products by Acute Neuronal Cell Death

2002 ◽  
Vol 383 (5) ◽  
pp. 785-791 ◽  
Author(s):  
Satavisha Dutta ◽  
Yuk Chun Chiu ◽  
Albert W. Probert ◽  
Kevin K.W. Wang
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuronal Injury ◽  
Nmda Receptor Antagonist ◽  
Breakdown Product ◽  
Calpain Inhibitor ◽  
Neural Cells

Abstract Activation of calpain results in the breakdown of α II spectrin (αfodrin), a neuronal cytoskeleton protein, which has previously been detected in various in vitro and in vivo neuronal injury models. In this study, a 150 kDa spectrin breakdown product (SBDP150) was found to be released into the cellconditioned media from SHSY5Y cells treated with the calcium channel opener maitotoxin (MTX). SBDP150 release can be readily quantified on immunoblot using an SBDP150- specific polyclonal antibody. Increase of SBDP150 also correlated with cell death in a timedependent manner. MDL28170, a selective calpain inhibitor, was the only protease inhibitor tested that significantly reduced MTXinduced SBDP150 release. The cellconditioned media of cerebellar granule neurons challenged with excitotoxins (NMDA and kainate) also exhibited a significant increase of SBDP150 that was attenuated by pretreatment with an NMDA receptor antagonist, R()-3-(2-carbopiperazine-4-yl)propyl-1- phosphonic acid (CPP), and MDL28170. In addition, hypoxic/hypoglycemic challenge of cerebrocortical cultures also resulted in SBDP150 liberation into the media. These results support the theory that an antibody based detection of SBDP150 in the cellconditioned media can be utilized to quantify injury to neural cells. Furthermore, SBDP150 may potentially be used as a surrogate biomarker for acute neuronal injury in clinical settings.

Degradation of mutant huntingtin via the ubiquitin/proteasome system is modulated by FE65

2012 ◽  
Vol 443 (3) ◽  
pp. 681-689 ◽  
Author(s):  
Wan Ning Vanessa Chow ◽  
Hon Wing Luk ◽  
Ho Yin Edwin Chan ◽  
Kwok-Fai Lau
Keyword(s):  
Cell Death ◽  
Degradation Mechanism ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Adaptor Protein ◽  
Ubiquitin Proteasome System ◽  
Exon 1 ◽  
Ubiquitin Proteasome

An unstable expansion of the polyglutamine repeat within exon 1 of the protein Htt (huntingtin) causes HD (Huntington's disease). Mounting evidence shows that accumulation of N-terminal mutant Htt fragments is the source of disruption of normal cellular processes which ultimately leads to neuronal cell death. Understanding the degradation mechanism of mutant Htt and improving its clearance has emerged as a new direction in developing therapeutic approaches to treat HD. In the present study we show that the brain-enriched adaptor protein FE65 is a novel interacting partner of Htt. The binding is mediated through WW–polyproline interaction and is dependent on the length of the polyglutamine tract. Interestingly, a reduction in mutant Htt protein level was observed in FE65-knockdown cells, and the process requires the UPS (ubiquitin/proteasome system). Moreover, the ubiquitination level of mutant Htt was found to be enhanced when FE65 is knocked down. Immunofluroescence staining revealed that FE65 associates with mutant Htt aggregates. Additionally, we demonstrated that overexpression of FE65 increases mutant Htt-induced cell death both in vitro and in vivo. These results suggest that FE65 facilitates the accumulation of mutant Htt in cells by preventing its degradation via the UPS, and thereby enhances the toxicity of mutant Htt.

Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals

2004 ◽  
Vol 123 (1-3) ◽  
pp. 51-59 ◽  
Author(s):  
Dóra Reglödi ◽  
Zsolt Fábián ◽  
Andrea Tamás ◽  
Andrea Lubics ◽  
József Szeberényi ◽  
...  
Keyword(s):  
Cell Death ◽  
Platelet Aggregation ◽  
Oxygen Radicals ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Reactive Oxygen

No effect of apolipoprotein E on neuronal cell death due to excitotoxic and apoptotic agents in vitro and neonatal hypoxic ischaemia in vivo

2000 ◽  
Vol 12 (7) ◽  
pp. 2235-2242 ◽  
Author(s):  
Corinne L. Lendon ◽  
Byung Hee Han ◽  
Kayvon Salimi ◽  
Anne M. Fagan ◽  
Maria I. Behrens ◽  
...  
Keyword(s):  
Cell Death ◽  
Apolipoprotein E ◽  
Neuronal Cell Death ◽  
Neuronal Cell

Influence of corticotrophin releasing factor on neuronal cell death in vitro and in vivo

2000 ◽  
Vol 881 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Mark W. Craighead ◽  
Herve Boutin ◽  
Kelly M.L. Middlehurst ◽  
Stuart M. Allan ◽  
Nigel Brooks ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Corticotrophin Releasing Factor

scholarly journals Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhongyuan Bao ◽  
Yinlong Liu ◽  
Binglin Chen ◽  
Zong Miao ◽  
Yiming Tu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Lipid Peroxidation ◽  
Cell Death ◽  
Brain Injury ◽  
Neuronal Degeneration ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Prokineticin 2

AbstractProkineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis.

scholarly journals Zinc Oxide Nanoparticles Induce Ferroptotic Neuronal Cell Death in vitro and in vivo

2020 ◽  
Vol Volume 15 ◽  
pp. 5299-5315
Author(s):  
Xia Qin ◽  
Qianghu Tang ◽  
Xuejun Jiang ◽  
Jun Zhang ◽  
Bin Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Oxide Nanoparticles

scholarly journals APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death

2001 ◽  
Vol 155 (2) ◽  
pp. 207-216 ◽  
Author(s):  
Andre Fortin ◽  
Sean P. Cregan ◽  
Jason G. MacLaurin ◽  
Neena Kushwaha ◽  
Emma S. Hickman ◽  
...  
Keyword(s):  
Cell Death ◽  
Binding Sites ◽  
Primary Cultures ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acute Injury ◽  
Mobility Shift ◽  
Transcriptional Target

p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5–6-fold upregulation of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced cell death, Apaf1 protein levels were increased. We addressed whether p53 directly regulates Apaf1 transcription via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic mobility shift assays demonstrated p53–DNA binding activity at both p53 consensus binding sequences in extracts obtained from neurons undergoing p53-induced cell death, but not in healthy control cultures or when p53 or the p53 binding sites were inactivated by mutation. In transient transfections in a neuronal cell line with p53 and Apaf1 promoter–luciferase constructs, p53 directly activated the Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene in neuronal cell death was evaluated by examining p53-induced apoptotic pathways in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin were significantly protected in the absence of Apaf1 relative to those derived from wild-type littermates. Together, these results demonstrate that Apaf1 is a key transcriptional target for p53 that plays a pivotal role in the regulation of apoptosis after neuronal injury.

scholarly journals The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina

2021 ◽  
Vol 22 (16) ◽  
pp. 9050
Author(s):  
Toshiyuki Oshitari
Keyword(s):  
Cell Death ◽  
Diabetic Retinopathy ◽  
Diabetic Neuropathy ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Axon Degeneration ◽  
Diabetic Patients ◽  
Therapeutic Approaches

Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina.

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