Cellular Injury and Death

2021 ◽  
pp. 209-214
Author(s):  
Nicolas N. Madigan ◽  
Nathan P. Staff
Keyword(s):  
Cell Death ◽  
Cellular Injury ◽  
Compensatory Mechanisms ◽  
Biochemical Processes ◽  
Cell Death Pathways ◽  
Severity Of Injury ◽  
Cellular Necrosis ◽  
Energy States ◽  
Nuclear Cell

Cell death occurs after an irreversible insult or stress overwhelms the cell’s compensatory mechanisms of homeostasis and repair. Cellular necrosis, apoptosis, and autophagy are increasingly understood to be interconnected biochemical processes that may coexist in vascular, inflammatory, and neurodegenerative conditions. Traditional classifications of cell death pathways are 1) necrosis; 2) programmed nuclear cell death, including apoptosis; and 3) autophagy. These processes occur in the context of variable cause and severity of injury, variable cellular metabolic and energy states, and variable fitness to compensate.

Development and Challenges of Nanotherapeutic Formulations for Targeting Mitochondrial Cell Death Pathways in Lung and Brain Degenerative Diseases

2020 ◽  
Vol 48 (3) ◽  
pp. 137-152
Author(s):  
Marko Manevski ◽  
Dinesh Devadoss ◽  
Ruben Castro ◽  
Lauren Delatorre ◽  
Adriana Yndart ◽  
...  
Keyword(s):  
Cell Death ◽  
Degenerative Diseases ◽  
Cell Death Pathways

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

scholarly journals The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B

2021 ◽  
Vol 22 (3) ◽  
pp. 1175
Author(s):  
Ryuta Inukai ◽  
Kanako Mori ◽  
Keiko Kuwata ◽  
Chihiro Suzuki ◽  
Masatoshi Maki ◽  
...  
Keyword(s):  
Cell Death ◽  
Essential Gene ◽  
Susceptibility Gene ◽  
Target Protein ◽  
Hek293 Cells ◽  
Dependent Manner ◽  
Gene Encoding ◽  
Endosomal Sorting ◽  
Cell Death Pathways ◽  
Apoptotic Protein

Apoptosis-linked gene 2 (ALG-2, also known as PDCD6) is a member of the penta-EF-hand (PEF) family of Ca2+-binding proteins. The murine gene encoding ALG-2 was originally reported to be an essential gene for apoptosis. However, the role of ALG-2 in cell death pathways has remained elusive. In the present study, we found that cell death-inducing p53 target protein 1 (CDIP1), a pro-apoptotic protein, interacts with ALG-2 in a Ca2+-dependent manner. Co-immunoprecipitation analysis of GFP-fused CDIP1 (GFP-CDIP1) revealed that GFP-CDIP1 associates with tumor susceptibility gene 101 (TSG101), a known target of ALG-2 and a subunit of endosomal sorting complex required for transport-I (ESCRT-I). ESCRT-I is a heterotetrameric complex composed of TSG101, VPS28, VPS37 and MVB12/UBAP1. Of diverse ESCRT-I species originating from four VPS37 isoforms (A, B, C, and D), CDIP1 preferentially associates with ESCRT-I containing VPS37B or VPS37C in part through the adaptor function of ALG-2. Overexpression of GFP-CDIP1 in HEK293 cells caused caspase-3/7-mediated cell death. In addition, the cell death was enhanced by co-expression of ALG-2 and ESCRT-I, indicating that ALG-2 likely promotes CDIP1-induced cell death by promoting the association between CDIP1 and ESCRT-I. We also found that CDIP1 binds to vesicle-associated membrane protein-associated protein (VAP)A and VAPB through the two phenylalanines in an acidic tract (FFAT)-like motif in the C-terminal region of CDIP1, mutations of which resulted in reduction of CDIP1-induced cell death. Therefore, our findings suggest that different expression levels of ALG-2, ESCRT-I subunits, VAPA and VAPB may have an impact on sensitivity of anticancer drugs associated with CDIP1 expression.

scholarly journals Long-Term Exposure to Nanosized TiO2 Triggers Stress Responses and Cell Death Pathways in Pulmonary Epithelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5349
Author(s):  
Mayes Alswady-Hoff ◽  
Johanna Samulin Erdem ◽  
Santosh Phuyal ◽  
Oskar Knittelfelder ◽  
Animesh Sharma ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Health Effects ◽  
Stress Responses ◽  
Cell Stress ◽  
Lipid Classes ◽  
Long Term Effects ◽  
Cell Death Pathways ◽  
Pulmonary Epithelial Cells

There is little in vitro data available on long-term effects of TiO2 exposure. Such data are important for improving the understanding of underlying mechanisms of adverse health effects of TiO2. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2) of TiO2 for 13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins involved in cell stress and genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO2.

Lateral size of graphene oxide determines differential cellular uptake and cell death pathways in Kupffer cells, LSECs, and hepatocytes

Nano Today ◽  
2021 ◽  
Vol 37 ◽  
pp. 101061
Author(s):  
Jiulong Li ◽  
Xiang Wang ◽  
Kuo-Ching Mei ◽  
Chong Hyun Chang ◽  
Jinhong Jiang ◽  
...  
Keyword(s):  
Cell Death ◽  
Graphene Oxide ◽  
Cellular Uptake ◽  
Kupffer Cells ◽  
Lateral Size ◽  
Cell Death Pathways

scholarly journals Cell Death Pathways and Viruses: Role of microRNAs

2021 ◽  
Author(s):  
Javid Sadri Nahand ◽  
Layla Shojaie ◽  
Seyed Amirreza Akhlagh ◽  
Mohammad Saeid Ebrahimi ◽  
Hamid Reza Mirzaei ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Death Pathways

scholarly journals Two Overlapping Domains of a Lyssavirus Matrix Protein That Acts on Different Cell Death Pathways

2010 ◽  
Vol 84 (19) ◽  
pp. 9897-9906 ◽  
Author(s):  
Florence Larrous ◽  
Alireza Gholami ◽  
Shahul Mouhamad ◽  
Jérôme Estaquier ◽  
Hervé Bourhy
Keyword(s):  
Cell Death ◽  
Amino Acid ◽  
Matrix Protein ◽  
Full Length ◽  
M Protein ◽  
Genotype 3 ◽  
Cell Death Pathways ◽  
Acid Fragment ◽  
M Proteins ◽  
Cellular Apoptosis

ABSTRACT The lyssavirus matrix (M) protein induces apoptosis. The regions of the M protein that are essential for triggering cell death pathways are not yet clearly defined. We therefore compared the M proteins from two viruses that have contrasting characteristics in terms of cellular apoptosis: a genotype 3 lyssavirus, Mokola virus (MOK), and a genotype 1 rabies virus isolated from a dog from Thailand (THA). We identified a 20-amino-acid fragment (corresponding to positions 67 to 86) that retained the cell death activities of the full-length M protein from MOK via both the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and inhibition of cytochrome c oxidase (CcO) activity. We found that the amino acids at positions 77 and 81 have an essential role in triggering these two cell death pathways. Directed mutagenesis demonstrated that the amino acid at position 77 affects CcO activity, whereas the amino acid at position 81 affects TRAIL-dependent apoptosis. Mutations in the full-length M protein that compromised induction of either of these two pathways resulted in delayed apoptosis compared with the time to apoptosis for the nonmutated control.

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