Apoptosis induction is an antiviral host response, however, influenza A virus (IAV) infection promotes host cell death. The nucleoprotein (NP) of IAV is known to contribute to viral pathogenesis, but its role in virus-induced host cell death was hitherto unknown. We observed that NP contributes to IAV infection induced cell death and heterologous expression of NP alone can induce apoptosis in human airway epithelial cells. The apoptotic effect of IAV NP was significant when compared with other known proapoptotic proteins of IAV. The cell death induced by IAV NP was executed through the intrinsic apoptosis pathway. We screened host cellular factors for those that may be targeted by NP for inducing apoptosis and identified human antiapoptotic protein Clusterin (CLU) as a novel interacting partner. The interaction between IAV NP and CLU was highly conserved and mediated through β-chain of the CLU protein. Also CLU was found to interact specifically with IAV NP and not with any other known apoptosis modulatory protein of IAV. CLU prevents induction of the intrinsic apoptosis pathway by binding to Bax and inhibiting its movement into the mitochondria. We found that the expression of IAV NP reduced the association between CLU and Bax in mammalian cells. Further, we observed that CLU overexpression attenuated NP-induced cell death and had a negative effect on IAV replication. Collectively, these findings indicate a new function for IAV NP in inducing host cell death and suggest a role for the host antiapoptotic protein CLU in this process.
Showing posts with label clusterin. Show all posts
Showing posts with label clusterin. Show all posts
Unglycosylated clusterin Variant accumulateS in the Endoplasmic Reticulum and induces cytotoxicity.
Clusterin is a stress-responsive and highly glycosylated secretory protein that plays cytoprotective role in most body fluids. In addition to extracellular clusterin, several intracellular clusterin variants that are rather cytotoxic have been recently uncovered under diverse pathological conditions. Although these variants revealed heterogeneity in their glycan modification, its significance in many diseases remains to be validated. Here, we found that clusterin is differentially metabolized by two well-characterized ER stress inducers. Thapsigargin induced retrotranslocation and rapid degradation of clusterin from the endoplasmic reticulum, whereas tunicamycin failed to degrade but rather retained clusterin in the endoplasmic reticulum. Important sorting determinant for these processes proved to be N-glycan moieties that are required for the prevention of terminal misfolding and aggregation of clusterin in the endoplasmic reticulum. This study provides a mechanistic insight into the generation of noble cytotoxic variant of intracellular clusterin and an idea about molecular pathogenesis of diseases associated with chronic endoplasmic reticulum stress, such as neurodegeneration.
Semen Clusterin Is a Novel DC-SIGN Ligand. [J Immunol. 2011] - PubMed - NCBI
DC-SIGN (CD209) is expressed on the surface of dendritic cells and macrophages. It is involved in the innate immune system and recognizes diverse pathogens ranging from parasites to viruses.
Serum Clusterin Levels are not increased in Presymptomatic Alzheimer's Disease.
Clusterin levels were increased in already existing Alzheimer's disease, but not pre-symptoms. Biomarkers are urgently needed in the ageing population, but unfortunately this is not one of them.
Risk factors: Alzheimer's :
KEGG pathways Alzheimer's Herpes simplex infection
Risk factors: Alzheimer's :
KEGG pathways Alzheimer's Herpes simplex infection
Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
This study confirmed APOE , clusterin , complement receptor 1 and PICALM, and also angiotensin converting enzyme ACE and cystatin CST3 as Alzheimer's disease risk factors
However, note that PICALM did not turn up positive in a chinese study Yu et al, 20101 supporting the notion that genetic associations may cluster in geographical hot and cold spots. See database
However, note that PICALM did not turn up positive in a chinese study Yu et al, 20101 supporting the notion that genetic associations may cluster in geographical hot and cold spots. See database
Proteomic analysis of plasma proteins in Japanese semisuper centenarians.
Paraoxonase/arylesterase 1 (PON 1) and apolipoprotein E were decreased, while haptoglobin β-chain, α(1)-microglobulin, and clusterin precursor were increased inthis study
Implication of the immune system in Alzheimer's disease: evidence from genome-wide pathway analysis.
Previous data from old-fashioned case-controls had already implicated a number of immune-related genes. Clusterin and complement receptor 1 also fall into this category See database
Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer's disease patients and in normal cohorts from Russian populations
Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer's disease patients and in normal cohorts from Russian populations
Negative data showing the herterogeneity of gene association studies
Association of the clusterin gene polymorphisms with type 2 diabetes mellitus.
Very interesting because of the asociation between diabetes and Alzheimer's disease
Multiple relationships between Herpes simplex and Alzheimer's disease susceptibility genes
A large number of Alzheimer's disease susceptibility genes, including APOE, Clusterin, PICALM and complement receptor 1 Carter 2010, as well as APP, BACE, gamma-secretase and many others, are intimately involved in the life cycle of Herpes simplex, an established risk factor for Alzheimer's disease as championed by Ruth Itzhaki's group and others.
More than this, Herpes simplex infection in mice causes entorhinal cortex and hippocampal degeneration, cerebral shrinkage and memory loss Armien et al, 2010. It also promotes tau phosphorylation Wozniak et al, 2009 and beta-amyloid deposition Wozniak et al, 2007. In other words, Alzheimer's disease.
There are no clinical trials, as yet, for antiviral agents.
More than this, Herpes simplex infection in mice causes entorhinal cortex and hippocampal degeneration, cerebral shrinkage and memory loss Armien et al, 2010. It also promotes tau phosphorylation Wozniak et al, 2009 and beta-amyloid deposition Wozniak et al, 2007. In other words, Alzheimer's disease.
There are no clinical trials, as yet, for antiviral agents.
Low Clusterin Levels in High-Density Lipoprotein Associate With Insulin Resistance, Obesity, and Dyslipoproteinemia.
Low Clusterin Levels in High-Density Lipoprotein Associate With Insulin Resistance, Obesity, and Dyslipoproteinemia.
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