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Toxic Proteins (toxic + protein)
Selected AbstractsAlcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic StudiesALCOHOLISM, Issue 2 2009Michael A. Collins In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions,pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, ,-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways. [source] Targeted cell-ablation in Xenopus embryos using the conditional, toxic viral protein M2(H37A)DEVELOPMENTAL DYNAMICS, Issue 8 2007Stuart J. Smith Abstract Harnessing toxic proteins to destroy selective cells in an embryo is an attractive method for exploring details of cell fate and cell,cell interdependency. However, no existing "suicide gene" system has proved suitable for aquatic vertebrates. We use the M2(H37A) toxic ion channel of the influenza-A virus to induce cell-ablations in Xenopus laevis. M2(H37A) RNA injected into blastomeres of early stage embryos causes death of their progeny by late-blastula stages. Moreover, M2(H37A) toxicity can be controlled using the M2 inhibitor rimantadine. We have tested the ablation system using transgenesis to target M2(H37A) expression to selected cells in the embryo. Using the myocardial MLC2 promoter, M2(H37A)-mediated cell death causes dramatic loss of cardiac structure and function by stage 39. With the LURP1 promoter, we induce cell-ablations of macrophages. These experiments demonstrate the effectiveness of M2(H37A)-ablation in Xenopus and its utility in monitoring the progression of developmental abnormalities during targeted cell death experiments. Developmental Dynamics 236:2159,2171, 2007. © 2007 Wiley-Liss, Inc. [source] Protein misfolding in neurodegenerative diseasesNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2004E. I. Agorogiannis A common pathogenic mechanism shared by diverse neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease, Huntington's disease and transmissible spongiform encephalopathies, may be altered protein homeostasis leading to protein misfolding and aggregation of a wide variety of different proteins in the form of insoluble fibrils. Mutations in the genes encoding protein constituents of these aggregates have been linked to the corresponding diseases, thus a reasonable scenario of pathogenesis was based on misfolding of a neurone-specific protein that forms insoluble fibrils that subsequently kill neuronal cells. However, during the past 5 years accumulating evidence has revealed the neurotoxic role of prefibrillar intermediate forms (soluble oligomers and protofibrils) produced during fibril formation. Many think these may be the predominant neurotoxic species, whereas microscopically visible fibrillar aggregates may not be toxic. Large protein aggregates may rather be simply inactive, or even represent a protective state that sequesters and inactivates toxic oligomers and protofibrils. Further understanding of the biochemical mechanisms involved in protein misfolding and fibrillization may optimize the planning of common therapeutic approaches for neurodegenerative diseases, directed towards reversal of protein misfolding, blockade of protein oligomerization and interference with the action of toxic proteins. [source] Differential analysis of Bacillus anthracis after pX01 plasmid curing and comprehensive data on Bacillus anthracis infection in macrophages and glial cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 20 2007Sung-Ha Park Abstract Bacillus anthracis is a gram-positive bacterial organism responsible for anthrax. This organism has two pathogenic plasmids: pX01 and pX02. The genetic function of pX01, which comprises about 198,kb, is not known, except for a region called the pathogenic island, which contains three genes,pag, lef, and cya,that code for three toxic proteins. A 2-D difference gel electrophoresis (2-D DIGE) system was used to verify the existence of proteins controlled by the pX01 plasmid, and protein regulation data were obtained using DeCyder software. A total of 1728 proteins were identified in the wild-type strain of this organism and 1684 in the pX01 plasmid. Twenty-seven of these proteins disappeared and eight appeared when the pX01 plasmid was removed. An additional 52 proteins were downregulated and 15 were upregulated when this plasmid was removed. A total of 102 proteins have been identified using the MALDI-TOF method of analysis, including 49 whose functions are unknown. Among these, 31 participate in metabolic processes, two in cellular processes, 15 in the processing of genetic information, and five in the processing of extracellular information. Another seven proteins participate in bacterial virulence and pathogenesis. We investigated the functions of these proteins in other bacteria, particularly the B. anthracis derivative H9041. Bacterial growth differed between pX01+/pX02+ B. anthracis and its pX01,/pX02+ derivative as did the cytotoxicity of macrophages infected by pX01+/pX02+ B. anthracis and the pX01,pX02+ derivative. We also found that S100B protein levels increased in the host infected with pX01+/pX02+ B. anthracis or its pX01,/pX02+ derivative. These data suggest that the pX01 plasmid plays a key role in the regulation of protein functions in B. anthracis. [source] Priming by airborne signals boosts direct and indirect resistance in maizeTHE PLANT JOURNAL, Issue 1 2007Jurriaan Ton Summary Plants counteract attack by herbivorous insects using a variety of inducible defence mechanisms. The production of toxic proteins and metabolites that instantly affect the herbivore's development are examples of direct induced defence. In addition, plants may release mixtures of volatile organic compounds (VOCs) that indirectly protect the plant by attracting natural enemies of the herbivore. Recent studies suggest that these VOCs can also prime nearby plants for enhanced induction of defence upon future insect attack. However, evidence that this defence priming causes reduced vulnerability to insects is sparse. Here we present molecular, chemical and behavioural evidence that VOC-induced priming leads to improved direct and indirect resistance in maize. A differential hybridization screen for inducible genes upon attack by Spodoptera littoralis caterpillars identified 10 defence-related genes that are responsive to wounding, jasmonic acid (JA), or caterpillar regurgitant. Exposure to VOCs from caterpillar-infested plants did not activate these genes directly, but primed a subset of them for earlier and/or stronger induction upon subsequent defence elicitation. This priming for defence-related gene expression correlated with reduced caterpillar feeding and development. Furthermore, exposure to caterpillar-induced VOCs primed for enhanced emissions of aromatic and terpenoid compounds. At the peak of this VOC emission, primed plants were significantly more attractive to parasitic Cotesia marginiventris waSPS. This study shows that VOC-induced priming targets a specific subset of JA-inducible genes, and links these responses at the molecular level to enhanced levels of direct and indirect resistance against insect attack. [source] Heterologous Protein Production from the Inducible MET25 Promoter in Saccharomyces cerevisiaeBIOTECHNOLOGY PROGRESS, Issue 2 2005Steven P. Solow Heterologous protein production late in Saccharomyces cerevisiae fermentations is often desirable because it may help avoid the unintentional selection of more rapidly growing, non-protein-expressing cells or allow for the expression of toxic proteins. Here, we describe the use of the MET25 promoter for the production of human serum albumin (HSA) and HSA-fusion proteins in S. cerevisiae. In media lacking methionine, the MET25 promoter yielded high expression levels of HSA and HSA fused to human glucagon, human growth hormone, human interferon ,, and human interleukin-2. More importantly, we have shown that this system can be used to delay heterologous protein production until late log phase of the growth of the culture and does not require the addition of an exogenous inducer. [source] | |||||||||||||