Missing mitochondrial Mpv17 gene function induces tissue-specific cell-death pathway in the degenerating inner ear

2012 ◽  
Vol 347 (2) ◽  
pp. 343-356 ◽  
Author(s):  
Angela-Maria Meyer zum Gottesberge ◽  
Thomas Massing ◽  
Stefan Hansen
Keyword(s):  
Cell Death ◽  
Inner Ear ◽  
Gene Function ◽  
Specific Cell ◽  
Tissue Specific ◽  
Cell Death Pathway

scholarly journals Identification of tissue-specific cell death using methylation patterns of circulating DNA

2016 ◽  
Vol 113 (13) ◽  
pp. E1826-E1834 ◽  
Author(s):  
Roni Lehmann-Werman ◽  
Daniel Neiman ◽  
Hai Zemmour ◽  
Joshua Moss ◽  
Judith Magenheim ◽  
...  
Keyword(s):  
Cell Death ◽  
Minimally Invasive ◽  
Dna Sequences ◽  
Cell Types ◽  
The Body ◽  
Specific Cell ◽  
Circulating Dna ◽  
Cell Type ◽  
Tissue Specific ◽  
Methylation Patterns

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.

scholarly journals The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

2010 ◽  
Vol 84 (10) ◽  
pp. 5108-5123 ◽  
Author(s):  
A. Louise McCormick ◽  
Linda Roback ◽  
Devon Livingston-Rosanoff ◽  
Courtney St. Clair
Keyword(s):  
Cell Death ◽  
Human Cytomegalovirus ◽  
Caspase 8 ◽  
Specific Cell ◽  
Macrophage Differentiation ◽  
Antiviral Responses ◽  
Cell Death Pathways ◽  
Cell Death Pathway ◽  
The Impact ◽  
Late Stages

ABSTRACT The cellular protease caspase-8 activates extrinsic apoptosis and also functions to promote monocyte-to-macrophage differentiation. Differentiation-induced alterations to antiviral caspase-8-dependent cell death pathways are unclear. Here, we show THP-1 monocyte-to-macrophage differentiation alters the specific cell death pathways activated in response to human cytomegalovirus (HCMV) infection. Employing viruses with mutations in UL36, the gene that encodes the viral inhibitor of caspase-8 activation (vICA), our data indicate that both caspase-dependent and -independent death pathways are activated in response to infection. Activation of caspase-dependent and -independent cell death responses restricted growth of vICA-deficient viruses, and vICA/pUL36 inhibited either response. Thus, these studies also reveal that the UL36 gene controls a caspase-independent cell death pathway. The impact of caspases on control of antiviral responses differed at early and late stages of macrophage differentiation. Early in differentiation, vICA-deficient virus-induced cell death was dependent on caspases and inhibited by the pan-caspase inhibitor z-VAD(OMe)-fluoromethyl ketone. In contrast, virus-induced death at late times of differentiation was caspase independent. Additional unlabeled and fluorescent inhibitors indicated that caspase-8 promoted death from within infected cells at early but not late stages of differentiation. These data highlight the multifunctional role of vICA/pUL36 as HCMV encounters various antiviral responses during macrophage differentiation.

scholarly journals Cell-specific expression of X-linked inhibitor of apoptosis in the anterior pituitary of streptozotocin-induced diabetic rats

2007 ◽  
Vol 192 (1) ◽  
pp. 215-227 ◽  
Author(s):  
Ana I Arroba ◽  
Alfonso M Lechuga-Sancho ◽  
Laura M Frago ◽  
Jesús Argente ◽  
Julie A Chowen
Keyword(s):  
Cell Death ◽  
Anterior Pituitary ◽  
Cell Types ◽  
Diabetic Rats ◽  
Inhibitor Of Apoptosis ◽  
Specific Cell ◽  
Cell Protection ◽  
Specific Expression ◽  
Cell Death Pathway ◽  
Apoptosis Protein

Cell death is increased in the anterior pituitary of poorly controlled diabetic rats, but anti-apoptotic mechanisms are also activated. We hypothesized that specific cell types are selectively protected against diabetes-induced cell death. To determine when anti-apoptotic mechanisms are activated, streptozotocin-induced diabetic rats were killed after 1, 4, 6 and 8 weeks of evolution. Anterior pituitaries were processed for western blot analysis to determine changes in the intrinsic cell death pathway and upstream kinases involved in cell protection mechanisms. An increase in cell death was detected by ELISA at 4 weeks of diabetes. TUNEL labelling demonstrated that this corresponded to death of primarily lactotrophs, a few somatotrophs, and no thyrotrophs, corticotrophs or gonadotrophs. Levels of phosphorylated (p) Akt were increased at 1 week of diabetes, while pERK1/2 levels increased at 4 weeks and pJNK at 6 weeks. Activation of caspase 3 decreased and anti-apoptotic members of the Bcl-2 protein family increased as early as 1 week after diabetes onset. These changes were coincident with increased IGF-I receptor levels. Levels of X-linked inhibitor of apoptosis protein (XIAP) increased significantly after 6 weeks of diabetes, as did activation of nuclear factor (NF)κB. Double immunohistochemistry indicated that XIAP was expressed in less than 1% of lactotrophs and gonadotrophs, approximately 50% of somatotrophs and more than 90% of corticotrophs and thyrotrophs. These results suggest that some cell survival mechanisms are rapidly activated in the anterior pituitary, even before increased cell death can be detected, while others are more delayed. Furthermore, both pituitary cell death and expression of protective mechanisms such as XIAP are cell-type specific.

A Cell Death Pathway Induced by Antibody-Mediated Cross-Linking of CD45 on Lymphocytes

2003 ◽  
Vol 23 (5-6) ◽  
pp. 421-440 ◽  
Author(s):  
Ann-Muriel Steff ◽  
Marylene Fortin ◽  
Fabianne Philippoussis ◽  
Sylvie Lesage ◽  
Chantal Arguin ◽  
...  
Keyword(s):  
Cell Death ◽  
Cross Linking ◽  
Cell Death Pathway ◽  
A Cell

Dynamical analysis of the programmed cell death pathway

2007 ◽  
Author(s):  
Luciano Carotenuto ◽  
Vincenza Pace ◽  
Dina Bellizzi ◽  
Giovanna De Benedictis
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dynamical Analysis ◽  
Cell Death Pathway
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