TITLE

TNF-α Contributes to Caspase-3 Independent Apoptosis in Neuroblastoma Cells: Role of NFAT

AUTHOR(S)
Álvarez, Susana; Blanco, Almudena; Fresno, Manuel; Muñoz-Fernández, Ma Ángeles
PUB. DATE
January 2011
SOURCE
PLoS ONE;2011, Vol. 6 Issue 1, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
There is increasing evidence that soluble factors in inflammatory central nervous system diseases not only regulate the inflammatory process but also directly influence electrophysiological membrane properties of neurons and astrocytes. In this context, the cytokine TNF-α (tumor necrosis factor-α) has complex injury promoting, as well as protective, effects on neuronal viability. Up-regulated TNF-α expression has also been found in various neurodegenerative diseases such as cerebral malaria, AIDS dementia, Alzheimer's disease, multiple sclerosis, and stroke, suggesting a potential pathogenic role of TNF-α in these diseases as well. We used the neuroblastoma cells SK-N-MC. Transcriptional activity was measured using luciferase reporter gene assays by using lipofectin. We performed cotransfection experiments of NFAT (nuclear factor of activated T cells) promoter constructed with a dominant negative version of NFAT (dn-NFAT). Cell death was performed by MTT (3-(4,5-dimethylthiazol-2-yl)5,5-diphenyltetrazolium bromide) and TUNEL assays. NFAT translocation was confirmed by Western blot. Involvement of NFAT in cell death was assessed by using VIVIT. P53, Fas-L, caspase-3, and caspase-9 expressions were carried out by Western blot. The mechanisms involved in TNF-α-induced cell death were assessed by using microarray analysis. TNF-α causes neuronal cell death in the absence of glia. TNF-α treatment results in nuclear translocation of NFAT through activation of calcineurin in a Ca2+ independent manner. We demonstrated the involvement of FasL/Fas, cytochrome c, and caspase-9 but the lack of caspase-3 activation. NB cell death was absolutely reverted in the presence of VIVIT, and partially diminished by anti-Fas treatment. These data demonstrate that TNF-α promotes FasL expression through NFAT activation in neuroblastoma cells and this event leads to increased apoptosis through independent caspase-3 activation.
ACCESSION #
59388076

 

Related Articles

  • TNF-a Inhibition as a Treatment Strategy for Neurodegenerative Disorders: New Drug Candidates and Targets. Tweedie, David; Sambamurti, Kumar; Greig, Nigel H. // Current Alzheimer Research;Oct2007, Vol. 4 Issue 4, p378 

    As the average ages of North Americans and Europeans continue to rise; similarly the incidence of �old age� associated illnesses likewise increases. Most notably among these ailments are conditions linked to dementia-related neurodegenerative disorders, such as Alzheimer's disease...

  • Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. Berk, Michael; Dean, Olivia; Drexhage, Hemmo; McNeil, John J.; Moylan, Steven; O'Neil, Adrienne; Davey, Christopher G.; Sanna, Livia; Maes, Michael // BMC Medicine;2013, Vol. 11 Issue 1, p1 

    There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD)....

  • TNF alpha affects the expression of GFAP and S100B: implications for Alzheimer’s disease. Edwards, M. M.; Robinson, S. R. // Journal of Neural Transmission;Nov2006, Vol. 113 Issue 11, p1709 

    Neurodegenerative disorders such as Alzheimer’s disease are characterized by increased intracellular and extracellular concentrations of the astrocytic proteins glial fibrillary acidic protein (GFAP) and S100B. The present study examined the potential contribution of tumor necrosis factor...

  • Ceramide sphingolipid signaling mediates Tumor Necrosis Factor (TNF)-dependent toxicity via caspase signaling in dopaminergic neurons. Martinez, Terina N.; Chen, Xi; Bandyopadhyay, Sibali; Merrill, Alfred H.; Tansey, Malú G. // Molecular Neurodegeneration;2012, Vol. 7 Issue 1, p45 

    Background: Dopaminergic (DA) neurons in the ventral midbrain selectively degenerate in Parkinson's disease (PD) in part because their oxidative environment in the substantia nigra (SN) may render them vulnerable to neuroinflammatory stimuli. Chronic inhibition of soluble Tumor Necrosis Factor...

  • Amyloid Deposition and Inflammation in APPswe/PS1dE9 Mouse Model of Alzheimer's Disease. Lingfei Ruan; Zhoujun Kang; Gang Pei; Yingying Le // Current Alzheimer Research;Dec2009, Vol. 6 Issue 6, p531 

    Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles associated with chronic inflammation. APPswe/PS1dE9 is an AD mouse model bearing mutant transgenes of amyloid precursor protein and presenilin-1. Amyloid deposition is present in this mouse model at early...

  • Role of astrocytes and microglia in central nervous system inflammation. Rothhammer, Veit; Quintana, Francisco // Seminars in Immunopathology;Nov2015, Vol. 37 Issue 6, p575 

    An introduction is presented in which the editor discusses various reports within the issue on topics including the diversity of central nervous system (CNS) myeloid cells during inflammation, the role of microglia and the inflammasome in Alzheimer's disease (AD), and the role of astrocytes as...

  • Perispinal Etanercept for Treatment of Alzheimer's Disease. Tobinick, Edward // Current Alzheimer Research;Dec2007, Vol. 4 Issue 5, p550 

    Background: Increasing basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of Alzheimer's Disease. Excess TNF-alpha, a cytokine with pleotropic effects in the CNS, has been suggested to be involved in the pathogenesis of AD. In...

  • Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases. Frankola, Kathryn A.; Greig, Nigel H.; Luo, Weiming; Tweedie, David // CNS & Neurological Disorders - Drug Targets;May2011, Vol. 10 Issue 3, p391 

    Inflammatory signals generated within the brain and peripheral nervous system direct diverse biological processes. Key amongst the inflammatory molecules is tumor necrosis factor-alpha (TNF-α), a potent pro-inflammatory cytokine that, via binding to its associated receptors, is considered to...

  • Fibrillar beta-amyloid peptide Aβ1-40 activates microglial proliferation via stimulating TNF-α release and H2O2 derived from NADPH oxidase: a cell culture study. Jekabsone, Aiste; Mander, Palwinder K.; Tickler, Anna; Sharpe, Martyn; Brown, Guy C. // Journal of Neuroinflammation;2006, Vol. 3, p1 

    Background: Alzheimer's disease is characterized by the accumulation of neuritic plaques, containing activated microglia and β-amyloid peptides (Aβ). Fibrillar Aβ can activate microglia, resulting in production of toxic and inflammatory mediators like hydrogen peroxide, nitric oxide,...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics