Search results for "chaperon"
showing 10 items of 358 documents
Chaperoning the <em>Mononegavirales</em>: Current Knowledge and Future Directions
2018
The order Mononegavirales harbors numerous viruses of significant relevance for human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins…
Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic …
2011
In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated wi…
Multiple Receptors Mediate apoJ-Dependent Clearance of Cellular Debris into Nonprofessional Phagocytes
2001
Phagocytosis of apoptotic, senescent, and dying cells by macrophages is a well characterized process. More recently it has been shown that in addition to macrophages vital neighboring cells in the affected tissue participate in the cellular clearance. While scavenger receptors have been shown to mediate uptake into macrophages, it is poorly understood how cellular debris is internalized by nonprofessional phagocytes. We here analyze the endocytic activity of vital fibroblasts and epithelial cells exposed to cellular debris and membrane remnants. We show a mutual stimulation in the endocytosis of debris and apolipoproteinJ (clusterin) in these cells. Experiments using RAP (receptor-associate…
Zebrafish as a Model for the Study of Chaperonopathies.
2016
There is considerable information on the clinical manifestations and mode of inheritance for many genetic chaperonopathies but little is known on the molecular mechanisms underlying the cell and tissue abnormalities that characterize them. This scarcity of knowledge is mostly due to the lack of appropriate animal models that mimic closely the human molecular, cellular, and histological characteristics. In this article we introduce zebrafish as a suitable model to study molecular and cellular mechanisms pertaining to human chaperonopathies. Genetic chaperonopathies manifest themselves from very early in life so it is necessary to examine the impact of mutant chaperone genes during developmen…
Thermostability of Two Cyanobacterial GrpE Thermosensors
2011
GrpE proteins act as co-chaperones for DnaK heat-shock proteins. The dimeric protein unfolds under heat stress conditions, which results in impaired interaction with a DnaK protein. Since interaction of GrpE with DnaK is crucial for the DnaK chaperone activity, GrpE proteins act as a thermosensor in bacteria. Here we have analyzed the thermostability and function of two GrpE homologs of the mesophilic cyanobacterium Synechocystis sp. PCC 6803 and of the thermophilic cyanobacterium Thermosynechococcus elongatus BP1. While in Synechocystis an N-terminal helix pair of the GrpE dimer appears to be the thermosensing domain and mainly mediates GrpE dimerization, the C-terminal four-helix bundle i…
Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations
2015
Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherich…
De Novo prion aggregates trigger autophagy in skeletal muscle
2014
ABSTRACT In certain sporadic, familial, and infectious prion diseases, the prion protein misfolds and aggregates in skeletal muscle in addition to the brain and spinal cord. In myocytes, prion aggregates accumulate intracellularly, yet little is known about clearance pathways. Here we investigated the clearance of prion aggregates in muscle of transgenic mice that develop prion disease de novo . In addition to neurodegeneration, aged mice developed a degenerative myopathy, with scattered myocytes containing ubiquitinated, intracellular prion inclusions that were adjacent to myocytes lacking inclusions. Myocytes also showed elevated levels of the endoplasmic reticulum chaperone Grp78/BiP, su…
Antitumor effects of dehydroxymethylepoxyquinomicin, a novel nuclear factor-kappaB inhibitor, in human liver cancer cells are mediated through a reac…
2009
Activation of the nuclear transcription factor-kappa B (NF-kappa B) has been implicated in liver tumorigenesis. We evaluated the effects of a novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in two human liver cancer cell lines HA22T/VGH and HuH-6. DHMEQ treatment dose dependently decreased the DNA-binding capacity of the NF-kappa B p65 subunit, inhibited cell growth and proliferation, and increased apoptosis as shown by caspase activation, release of cytochrome c, poly(ADP-ribose) polymerase cleavage, and down-regulation of survivin. DHMEQ also induced a dose-dependent activation of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling, …
Heat shock proteins: essential proteins for apoptosis regulation
2008
Abstract Many different external and intrinsic apoptotic stimuli induce the accumulation in the cells of a set of proteins known as stress or heat shock proteins (HSPs). HSPs are conserved proteins present in both prokaryotes and eukaryotes. These proteins play an essential role as molecular chaperones by assisting the correct folding of nascent and stress-accumulated misfolded proteins, and by preventing their aggregation. HSPs have a protective function, that is they allow the cells to survive to otherwise lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of HSPs. Several of these proteins have demonstrated to directly interact with compo…
Apoptotic Cell Debris and Phosphatidylserine-Containing Lipid Vesicles Induce Apolipoprotein J (Clusterin) Gene Expression in Vital Fibroblasts
2001
The molecular events in cells undergoing programmed cell death (apoptosis) are well studied; however, the response of the surviving neighbor cells to local cell death is largely uncharacterized. Apolipoprotein J (clusterin) is an 80-kDa glycoprotein that has been implied in cytoprotection of the vital cells, presumably by assisting in the clearance of apoptotic vesicles and membrane remnants. Its mRNA is specifically up-regulated in the vital cells of apoptotic tissues. The molecular mechanisms, however, leading to this response are not known. We here show that exposure of vital fibroblasts to apoptotic vesicles, disrupted vital cells, and trypsin-treated membrane remnants induces apoJ mRNA…