Effect of proteins from the spirochete Borrelia burgdorferi sensu lato on myelinated nerve excitability.
Rodionova NN, Brazhe NA, Brazhe AR, Kharitonenkov IG, Maksimov GV. Biological Faculty, M. V. Lomonosov Moscow State University. [email protected]
We studied the effect of spirochete Borrelia burgdorferi sensu lato cell membrane proteins on excitability of myelinated nerve fiber.
It was found that cell surface proteins of spirochetes B. burgdorferi s. s. bind to Ranvier nodes of the axon and to Schwann cells.
Binding of B. burgdorferi s. s. and B. garinii to the nerve fiber modulates the amplitude and conduction velocity of the action potential, while B. afzelii had no effect on these parameters.
The decrease in the spike amplitude and conduction velocity during sorption of B. burgdorferi s. s. or cell wall proteins was accompanied by desorption of membrane-bound calcium.
PMID: 18019007
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I think it means that proteins from certain strains of the Lyme bacteria bind to the receptor sites and block the action of calcium on the nerves???
I'm confused -- isn't calcium excitatory and magnesium relaxing to nerves. Maybe there is more free calcium which is exciting the nerves?
Too tired to reason this out, but this research seems to be really significant.
Bea Seibert
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CaliforniaLyme
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Cascade!!! It is the beginning of a cascade effect!!!! **************************************** A Study of Demyelination of Nerve Fibers Using Dynamic Phase Contrast Microscopy Journal Bulletin of Experimental Biology and Medicine Publisher Springer New York ISSN 0007-4888 (Print) 1573-8221 (Online) Issue Volume 131, Number 5 / May, 2001 DOI 10.1023/A:1017923915116 Pages 457-460 Subject Collection Biomedical and Life Sciences
A Study of Demyelination of Nerve Fibers Using Dynamic Phase Contrast Microscopy G. V. Maksimov1 , S. L. Nikandrov1 , E. S. Lazareva1 , V. P. Tychinskii1 and A. B. Rubin1
(1) Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow Institute of Radio Engineering, Electronics, and Automatics, Russia
Abstract
Dynamic phase microscopy was used for evaluation of changes in myelinated axon segment in the paranodal region of nerve fibers during demyelination.
Normally paranodal myelin sheath is characterized by regular oscillations of the optical path difference with frequences of 4.2 and 6.7 Hz.
Demyelination decreased the amplitude and conduction velocity in nerve fibers and shifted the characteristic frequencies of optical path difference oscillations to 2.8, 3.2, and 11 Hz.
These shifts of optical path difference frequencies probably resulted from disturbances in the state of charged phospholipids and
*************a decrease in the level of bound Ca2+ during demyelination of nerve fiber.
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You have to have bound calcium to have a relaxed muscle so RIGHT here is the beginning of TWITCHES! Free calcium ions initiate CONTRACTIONS!!!! MUSCLE CONTRACTIONS!!
TWITCHES!!!! THIS IS WHY WE TWITCH!!!!
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Localization of calcium in nerve fibers
S. Y. Chan, S. Ochs *, R. A. Jersild Jr. * Indiana University School of Medicine, Indianapolis, Indiana
*Correspondence to S. Ochs, Department of Physiology, Indiana University School of Medicine, Indianapolis, Indiana
*Correspondence to R. A. Jersild Jr., Department of Anatomy, Indiana University School of Medicine, Indianapolis, Indiana
Abstract Using the desheathed nerve preparation, a pyroantimonate precipitation method was used to examine the distribution of electron-dense particles seen in various organelles of the nerve fibers following exposure of nerve to various levels of Ca2+ in vitro. The presence of Ca2+ in the electron-dense particles was indicated by their extraction with EGTA and by the use of energy-dispersive X-ray microanalysis.
In normal Ringer or in a Ca2+-free medium, electron-dense particles were seen associated with the outer membrane of the mitochondria, with the smooth endoplasmic reticulum (SER), along the axolemma and yet others scattered throughout the axoplasm.
When nerves were incubated in media containing higher than normal concentrations of 20-60 mM Ca2+, an increase in the number of such electron-dense particles was seen in the axoplasm and within the mitochondrial matrix. Nerves loaded with a high concentration of 60mM Ca2+ could be depleted of these particles after transfer to a Ca2+-free or low Ca2+ Ringer medium.
The sequenstration of Ca2+ in axonal organelles is discussed with respect to Ca2+-regulatory mechanisms in the axon needed to maintain a low level of Ca2+ which is optimal for the support of axoplasmic transport.
-------------------------------------------------------------------------------- Received: 5 February 1982; Revised: 12 July 1983 Digital Object Identifier (DOI)
10.1002/neu.480150203 About DOI
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And mitochrondial dysfunction is involved with ALS- and calcium is also very important to mitochrondrial functioN!! Look at this article re calicum- the difference is FREE calcium- not bound calcium!!! And ALSers have high calcium levels- free levels- which would match teh mitchondrial dysfunction!!!
QUOTE: ``Calcium levels went up like never before, which is unusual, because mitochrondria typically are able to tightly maintain a low level of calcium,'' said Ghafourifar, also an investigator in the Davis Heart and Lung Research Institute. That glut of calcium, in turn, triggered an enzyme to begin churning out toxic levels of the free radical nitric oxide - much more than the mitochondria could handle. And that excess of nitric oxide led to the release of a mitochondrial protein that sends the death signal to the cell.
***************************** Mitochondria Send Death Signal To Cardiac Cells, Study Shows
ScienceDaily (Nov. 10, 2007) -- Scientists have determined how cardiac cells die just as emergency treatments restore blood flow to a heart in distress, a paradox that has long puzzled doctors who are able to relieve pain in patients suffering from blocked arteries but can't stop the damage caused by the renewed rush of blood.
The discovery may lead to new ways to save that dying tissue.
It is the stoppage of blood flow and resulting loss of oxygen to the heart that causes chest pain during cardiac events. Clinicians' first order of business is restoring that flow with medicine or other noninvasive procedures, or even an invasive procedure, such as placement of a stent or balloon to open a blocked vessel.
But the rush of blood - and the oxygen it carries - that restores a heart's beat and relieves the pain can also damage tissue and weaken the heart's function because cardiac cells die in the process. And like brain cells, cardiac cells take a long time for the body to replace, so the damage is difficult to repair.
Researchers at Ohio State University Medical Center have traced this cell-death signal to the mitochondria, the principal energy source of cells, through a specialized technique. In experiments, cardiac cell mitochondria were isolated and subjected to ischemia and reperfusion - the blockage and restart of blood flow. The researchers hope that identifying the origin of the cell-death signal will improve the chances of finding a way to stop the signal, reducing the damage associated with restored blood flow to the heart.
``This form of cardiac cell death is a major medical and health issue. The patient has severe pain from the loss of blood flow and oxygen to the heart, so we cannot do anything other than clear that artery to restore the blood and oxygen. But when that is done, the patient loses cardiac cells. It's a paradox,'' said senior study author Pedram Ghafourifar, associate professor of surgery and pharmacology and director of basic science research in the division of vascular surgery at Ohio State 's Medical Center.
``The mitochondria have been suspected in this process, but to date, we haven't known for sure.''
Ghafourifar's lab developed a technique allowing researchers to watch isolated mitochondria in real time during this process. Using chemical probes and a novel technique called dual-wavelengths excitation spectrophotofluorometry, they saw that after the mitochrondria were subjected to ischemia followed by reoxygenation, a boost of calcium occurred in the mitochondria.
``Calcium levels went up like never before, which is unusual, because mitochrondria typically are able to tightly maintain a low level of calcium,'' said Ghafourifar, also an investigator in the Davis Heart and Lung Research Institute. That glut of calcium, in turn, triggered an enzyme to begin churning out toxic levels of the free radical nitric oxide - much more than the mitochondria could handle. And that excess of nitric oxide led to the release of a mitochondrial protein that sends the death signal to the cell.
The enzyme at work in this process is called mitochondrial nitric oxide synthase, discovered and reported by Ghafourifar's lab in 1997. Because researchers don't know the cause of the calcium increase during reoxygenation of the heart, Ghafourifar and his colleagues have focused on the enzyme as a therapeutic target to stop the production of nitric oxide that leads to cell death.
``The next immediate step is finding whether we can inhibit this enzyme so it doesn't generate excess nitric oxide during the reoxygenation phase,'' Ghafourifar said. ``We're trying to develop experimental drugs that can be delivered at the time of reperfusion or just before. Some seem to be successful at selectively inhibiting the enzyme.''
The experimental therapies will soon be tested in animal studies.
The identification of the enzyme as a target to stop cell death could influence a range of therapeutic options, Ghafourifar said, by applying to disease processes characterized by cell death, or, in the case of cancer, the refusal of cells to die when they should.
``Cell death is involved in a variety of diseases that don't seem to be related,'' he said. ``In cancer, cells do not die. In Parkinson's and Alzheimer's disease, cells die earlier than we want them to. If we figure out how cell death happens, we can put up a fight against a number of diseases.''
The results were published in the October issue of the Journal of Molecular and Cellular Cardiology.
Adapted from materials provided by Ohio State University.
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My reading of it-
So Lyme spirochetes free calcium which stimulates mitochondria to kill cells-
and free calcium ions- cause- TWITCHES- muscle contractions!!!!!! as a symptom of this process/ cascade effect!!!
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of course it dysregulates magnesium too-
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Vermont_Lymie
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Sarah,
So,
What would bind the free calcium ions?
(Not that it will be that simple, probably....)
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Maybe this explains the constant twitching.
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Yes- it does- in this model- of course there is probably a range of modeled infection- but I honestly would never have thought it was so close in terms of cause & effect- I would have thought that bb does x which does y wihch does z which does t which causes twitching- but it is very close here- it is Bb does x which causes twitchinG! wow!!! That is amazing!!!!!!!!!!!
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1998
From: University of Pittsburgh Medical Center
Pitt Neuroscientists Uncover Mechanism For Neuron Death, Counter Long-Held Assumptions About This Process
PITTSBURGH, Sept. 4 -- An influx of calcium specifically into mitochondria appears to trigger the death of neurons exposed to glutamate, a neurotransmitter that proves toxic when it's overproduced in traumatic brain injury and stroke. This research finding, presented by University of Pittsburgh investigators in the September issue of Nature Neuroscience, derails a long-held assumption that high concentrations of calcium within a cell's cytoplasm - and not in the mitochondria -- causes cells to die.
"In our research, we found that neurons can accumulate high amounts of calcium inside the cytoplasm without breaking down. It's only when large amounts of calcium flow into mitochondria that neurons die," said Ian Reynolds, Ph.D., associate professor of pharmacology at the University of Pittsburgh School Medicine.
"This information clearly shows that we should consider designing drugs to target mitochondria to prevent or intervene in glutamate-induced neuronal damage," said Dr. Reynolds. Specific calcium channels on the surface of mitochrondria may prove one important target for drug design, he added.
As with all living cells, a neuron consists of a cell membrane enclosing fluid cytoplasm. Within the cytoplasm are intracellular organelles, including mitochondria. Mitochondria are kidney-shaped organelles that have their own DNA and which produce energy for cells to function.
Glutamate works by binding to receptors on the surface of a neuron. This binding activates an influx of calcium that triggers the neuron to release additional glutamate, which stimulates other neurons, resulting in neurotransmission. Sometimes, however, injured or diseased nerves release too much glutamate. Excess glutamate over-stimulates neurons. The resultant neurotoxicity causes cell death.
Traditionally, neuroscientists have thought that too much calcium would perturb calcium-sensitive enzymes within the cytoplasm. These enzymes are critical to the function of a neuron. Several research teams have suggested that the disturbance of these enzymes, rather than any problems with mitochondria, mediate cell death.
"We discovered that neurons can tolerate 20 times more calcium than what was formerly believed to be lethal, as long as this calcium doesn't get inside mitochondria," said Amy Stout, first author on the paper and a post-doctoral student investigator in Dr. Reynold's lab.
Calcium influx into mitochondria appears to trip a death switch for neurons, whereas changes in calcium-sensitive enzymes within the cytoplasm are like dimmer switches that change the health of a neuron by degrees, according to Dr. Reynolds.
In their studies, the investigators cultured neurons from the forebrains of rats and exposed them to varying concentrations of calcium. In some cases, they also exposed the cells to chemicals that block the uptake of calcium by mitochondria. Cells that received high levels of calcium but no mitochondrial blockers died. Cells that were exposed to high calcium concentrations and mitochondrial calcium blockers lived.
Calcium ultimately may ruin mitochondria through a number of mechanisms, according to Dr. Reynolds. Normally, mitochondria can absorb excess calcium from cells. But constantly cycling calcium out of the cytoplasm may sap mitochondria of energy they normally produce to charge cells. Calcium influx also can spur the formation of free radicals that damage mitochondrial DNA or inevitably rip holes in the mitochondrial membrane.
Together with Teresa Hasting, Ph.D., assistant professor of neurology at Pitt, Dr. Reynolds recently received a more-than $1 million federal grant to study mitochondrial responses in neuronal injury.
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COntraction of muscles- see Elton David Aberles work page Principles of Meat Science 73-74 re muscle contractions and the role of calcium and magnesium- they have to be in balance for muscle to be relaxed- and be properly sequestered, not free- intersting read-
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QUOTE, ALS page-
Mitochondrial abnormalities. The mitochondria are the powerhouses, or energy factories, of cells. They are responsible for many aspects of proper cellular function, including the production of ATP, the scavenging of radical oxygen species, and the maintenance of intracellular calcium concentrations. In ALS patients, changes in mitochondria have been identified (Menzies FM et al 2002).
Mitochondrial abnormalities can directly lead to free radical production or increased calcium levels between cells.
Additionally, because proper mitochondrial function is so essential, other processes, as yet unidentified, could be altered when mitochondrial health is impaired (Fosslien E 2001).
Supplements that support healthy mitochondrial function may help stabilize mitochondrial health. Supplements that have been proven to support the mitochondria include coenzyme Q10 (CoQ10), creatine, and Ginkgo biloba.
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And because TBE viruses are pH mediated this is why BABESIOSIS is often a coinfection- because BABESIOSIS (especially WA1) makes the body more ACIDIC!!!!!!!!!!!!!!!!!! (my hypothesis*)!!!!
So it begins the activation and you have all the free calcium ions going around ruining mitochondria and killing neurons and you have so many cascades going on that even killing the Lyme spirochetes just kill the spirochetes but the TBE virus= because of FURIN- and FURIN is incited by the calcium- so it is ALMOST TOO LATE!!! The LYme HELPS the TBE virus! Because furin is calcium mediated=
If I began to have ALS type symptoms I would go to an alkaline diet, drink Ledum tea, get either IV Rocepihn or IM Bicillin- ************************************ Wikipedia FURIN- Rock forever!!" -- Kiran Thyagaraja [Hide this message]
[Show more] Furin From Wikipedia, the free encyclopedia Jump to: navigation, search
Furin (paired basic amino acid cleaving enzyme)
PDB rendering based on 1p8j. Available structures: 1p8j Identifiers Symbol(s) FURIN; FUR; PACE; PCSK3; SPC1 External IDs OMIM: 136950 MGI: 97513 Homologene: 1930 [show]Gene Ontology Molecular Function: * furin activity * subtilase activity * calcium ion binding * protein binding * peptidase activity
Cellular Component: * Golgi apparatus * membrane * integral to membrane * trans-Golgi network transport vesicle
Orthologs Human Mouse Entrez 5045 18550 Ensembl ENSG00000140564 ENSMUSG00000030530 Uniprot P09958 Q6GTN6 Refseq NM_002569 (mRNA) NP_002560 (protein) XM_980423 (mRNA) XP_985517 (protein) Location Chr 15: 89.21 - 89.23 Mb Chr 7: 80.26 - 80.28 Mb Pubmed search [1] [2] Furin (paired basic amino acid cleaving enzyme), also known as FURIN, is a human gene.
The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a calcium-dependent serine endoprotease that can efficiently cleave precursor proteins at their paired basic amino acid processing sites. Some of its substrates are: proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. It is also thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene is thought to play a role in tumor progression. The use of alternate polyadenylation sites has been found for this gene.[1]
Furin is enriched in the Golgi apparatus, where it functions to cleave other proteins into their mature/active forms. Furin cleaves proteins just downstream of a basic amino acid target sequence (canonically, Arg-X-(Arg/Lys) -Arg'). In addition to processing cellular precursor proteins, furin is also utilized by a number of pathogens. For example, the envelope proteins of viruses such as HIV, influenza and dengue fever viruses must be cleaved by furin or furin-like proteases to become fully functional. Anthrax toxin, Pseudomonas exotoxin, and papillomaviruses must be processed by furin during their initial entry into host cells. Inhibitors of furin are under consideration as therapeutic agents for treating anthrax infection.
Furin is also known as PACE, Paired basic Amino acid Cleaving Enzyme. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR (FES Upstream Region) and therefore the protein was named furin. _))))))))))))))))))))))))))))))))))))))))))
Journal List > J Virol > v.71(11); Nov 1997 Summary Selected References PDF (627K) Contents Archive Journal Homepage Related material: PubMed recordPubMed related artsPubMed LinkOutGeneGEO ProfilesSubstance
PubMed articles by: Stadler, K. Allison, S. Schalich, J. Heinz, F. J Virol. 1997 November; 71(11): 8475-8481. Copyright notice Proteolytic activation of tick-borne encephalitis virus by furin. K Stadler, S L Allison, J Schalich, and F X Heinz Institute of Virology, University of Vienna, Austria. This article has been cited by other articles in PMC.
AbstractFlaviviruses are assembled intracellularly in an immature form containing heterodimers of two envelope proteins, E and prM. Shortly before the virion exits the cell, prM is cleaved by a cellular enzyme, and this processing step can be blocked by treatment with agents that raise the pH of exocytic compartments. We carried out in vivo and in vitro studies with tick-borne encephalitis (TBE) virus to investigate the possible role of furin in this process as well as the functional consequences of prM cleavage. We found that prM in immature virions can be correctly cleaved in vitro by recombinant bovine furin but that efficient cleavage occurs only after exposure of the virion to mildly acidic pH. The data suggest that exposure to an acidic environment induces an irreversible structural change that renders the cleavage site accessible to the enzyme. Cleavage by furin in vitro resulted in biological activation, as shown by a 100-fold increase in specific infectivity, the acquisition of membrane fusion and hemagglutination activity, and the ability of the envelope proteins to undergo low-pH-induced structural rearrangements characteristic of mature virions. In vivo, prM cleavage was blocked by a furin inhibitor, and infection of the furin-deficient cell line LoVo yielded only immature virions, suggesting that furin is essential for cleavage activation of flaviviruses.
Full TextThe Full Text of this article is available as a PDF (627K).Selected ReferencesThese references are in PubMed. This may not be the complete list of references from this article. Allison SL, Schalich J, Stiasny K, Mandl CW, Kunz C, Heinz FX. Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol. 1995 Feb;69(2):695-700. [PubMed] Allison SL, Stadler K, Mandl CW, Kunz C, Heinz FX. Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form. J Virol. 1995 Sep;69(9):5816-5820. [PubMed] Anderson RG, Orci L. A view of acidic intracellular compartments. J Cell Biol. 1988 Mar;106(3):539-543. [PubMed] Bosshart H, Humphrey J, Deignan E, Davidson J, Drazba J, Yuan L, Oorschot V, Peters PJ, Bonifacino JS. The cytoplasmic domain mediates localization of furin to the trans-Golgi network en route to the endosomal/lysosomal system. J Cell Biol. 1994 Sep;126(5):1157-1172. [PubMed] Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 1990;44:649-688. [PubMed] CLARKE DH, CASALS J. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. Am J Trop Med Hyg. 1958 Sep;7(5):561-573. [PubMed] Denault JB, Leduc R. Furin/PACE/SPC1: a convertase involved in exocytic and endocytic processing of precursor proteins. FEBS Lett. 1996 Jan 29;379(2):113-116. [PubMed] Guirakhoo F, Bolin RA, Roehrig JT. The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein. Virology. 1992 Dec;191(2):921-931. [PubMed] Guirakhoo F, Heinz FX, Mandl CW, Holzmann H, Kunz C. Fusion activity of flaviviruses: comparison of mature and immature (prM-containing) tick-borne encephalitis virions. J Gen Virol. 1991 Jun;72 (:1323-1329. [PubMed] Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992 Nov 26;360(6402):358-361. [PubMed] Heinz FX, Kunz C. Homogeneity of the structural glycoprotein from European isolates of tick-borne encephalitis virus: comparison with other flaviviruses. J Gen Virol. 1981 Dec;57(Pt 2):263-274. [PubMed] Heinz FX, Stiasny K, P�schner-Auer G, Holzmann H, Allison SL, Mandl CW, Kunz C. Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM. Virology. 1994 Jan;198(1):109-117. [PubMed] Holzmann H, Stiasny K, Ecker M, Kunz C, Heinz FX. Characterization of monoclonal antibody-escape mutants of tick-borne encephalitis virus with reduced neuroinvasiveness in mice. J Gen Virol. 1997 Jan;78(Pt 1):31-37. [PubMed] Horimoto T, Nakayama K, Smeekens SP, Kawaoka Y. Proprotein-processing endoproteases PC6 and furin both activate hemagglutinin of virulent avian influenza viruses. J Virol. 1994 Sep;68(9):6074-6078. [PubMed] Kantanen ML, Leinikki P, Kuismanen E. Endoproteolytic cleavage of HIV-1 gp160 envelope precursor occurs after exit from the trans-Golgi network (TGN). Arch Virol. 1995;140(8):1441-1449. [PubMed] Laemmli UK, Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575-599. [PubMed] Lobigs M, Garoff H. Fusion function of the Semliki Forest virus spike is activated by proteolytic cleavage of the envelope glycoprotein precursor p62. J Virol. 1990 Mar;64(3):1233-1240. [PubMed] Mandl CW, Heinz FX, Kunz C. Sequence of the structural proteins of tick-borne encephalitis virus (western subtype) and comparative analysis with other flaviviruses. Virology. 1988 Sep;166(1):197-205. [PubMed] Molloy SS, Bresnahan PA, Leppla SH, Klimpel KR, Thomas G. Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. J Biol Chem. 1992 Aug 15;267(23):16396-16402. [PubMed] Molloy SS, Thomas L, VanSlyke JK, Stenberg PE, Thomas G. Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface. EMBO J. 1994 Jan 1;13(1):18-33. [PubMed] Murray JM, Aaskov JG, Wright PJ. Processing of the dengue virus type 2 proteins prM and C-prM. J Gen Virol. 1993 Feb;74 (:175-182. [PubMed] Ohnishi Y, Shioda T, Nakayama K, Iwata S, Gotoh B, Hamaguchi M, Nagai Y. A furin-defective cell line is able to process correctly the gp160 of human immunodeficiency virus type 1. J Virol. 1994 Jun;68(6):4075-4079. [PubMed] Ohuchi M, Cramer A, Vey M, Ohuchi R, Garten W, Klenk HD. Rescue of vector-expressed fowl plague virus hemagglutinin in biologically active form by acidotropic agents and coexpressed M2 protein. J Virol. 1994 Feb;68(2):920-926. [PubMed] Ortmann D, Ohuchi M, Angliker H, Shaw E, Garten W, Klenk HD. Proteolytic cleavage of wild type and mutants of the F protein of human parainfluenza virus type 3 by two subtilisin-like endoproteases, furin and Kex2. J Virol. 1994 Apr;68(4):2772-2776. [PubMed] Randolph VB, Winkler G, Stollar V. Acidotropic amines inhibit proteolytic processing of flavivirus prM protein. Virology. 1990 Feb;174(2):450-458. [PubMed] Salminen A, Wahlberg JM, Lobigs M, Liljestr�m P, Garoff H. Membrane fusion process of Semliki Forest virus. II: Cleavage-dependent reorganization of the spike protein complex controls virus entry. J Cell Biol. 1992 Jan;116(2):349-357. [PubMed] Sariola M, Saraste J, Kuismanen E. Communication of post-Golgi elements with early endocytic pathway: regulation of endoproteolytic cleavage of Semliki Forest virus p62 precursor. J Cell Sci. 1995 Jun;108 (:2465-2475. [PubMed] Sch�fer W, Stroh A, Bergh�fer S, Seiler J, Vey M, Kruse ML, Kern HF, Klenk HD, Garten W. Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin. EMBO J. 1995 Jun 1;14(11):2424-2435. [PubMed] Schalich J, Allison SL, Stiasny K, Mandl CW, Kunz C, Heinz FX. Recombinant subviral particles from tick-borne encephalitis virus are fusogenic and provide a model system for studying flavivirus envelope glycoprotein functions. J Virol. 1996 Jul;70(7):4549-4557. [PubMed] Seksek O, Biwersi J, Verkman AS. Direct measurement of trans-Golgi pH in living cells and regulation by second messengers. J Biol Chem. 1995 Mar 10;270(10):4967-4970. [PubMed] Shapiro D, Brandt WE, Russell PK. Change involving a viral membrane glycoprotein during morphogenesis of group B arboviruses. Virology. 1972 Dec;50(3):906-911. [PubMed] Smeekens SP. Processing of protein precursors by a novel family of subtilisin-related mammalian endoproteases. Biotechnology (N Y). 1993 Feb;11(2):182-186. [PubMed] Stieneke-Gr�ber A, Vey M, Angliker H, Shaw E, Thomas G, Roberts C, Klenk HD, Garten W. Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO J. 1992 Jul;11(7):2407-2414. [PubMed] Takahashi S, Kasai K, Hatsuzawa K, Kitamura N, Misumi Y, Ikehara Y, Murakami K, Nakayama K. A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1019-1026. [PubMed] Takahashi S, Nakagawa T, Kasai K, Banno T, Duguay SJ, Van de Ven WJ, Murakami K, Nakayama K. A second mutant allele of furin in the processing-incompetent cell line, LoVo. Evidence for involvement of the homo B domain in autocatalytic activation. J Biol Chem. 1995 Nov 3;270(44):26565-26569. [PubMed] Vey M, Sch�fer W, Bergh�fer S, Klenk HD, Garten W. Maturation of the trans-Golgi network protease furin: compartmentalization of propeptide removal, substrate cleavage, and COOH-terminal truncation. J Cell Biol. 1994 Dec;127(6 Pt 2):1829-1842. [PubMed] Vey M, Sch�fer W, Reis B, Ohuchi R, Britt W, Garten W, Klenk HD, Radsak K. Proteolytic processing of human cytomegalovirus glycoprotein B (gpUL55) is mediated by the human endoprotease furin. Virology. 1995 Jan 10;206(1):746-749. [PubMed] Vidricaire G, Denault JB, Leduc R. Characterization of a secreted form of human furin endoprotease. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1011-1018. [PubMed] Wahlberg JM, Boere WA, Garoff H. The heterodimeric association between the membrane proteins of Semliki Forest virus changes its sensitivity to low pH during virus maturation. J Virol. 1989 Dec;63(12):4991-4997. [PubMed] Wahlberg JM, Bron R, Wilschut J, Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309-7318. [PubMed] Watson DG, Moehring JM, Moehring TJ. A mutant CHO-K1 strain with resistance to Pseudomonas exotoxin A and alphaviruses fails to cleave Sindbis virus glycoprotein PE2. J Virol. 1991 May;65(5):2332-2339. [PubMed] Wengler G, Wengler G. Cell-associated West Nile flavivirus is covered with E+pre-M protein heterodimers which are destroyed and reorganized by proteolytic cleavage during virus release. J Virol. 1989 Jun;63(6):2521-2526. [PubMed] White JM. Viral and cellular membrane fusion proteins. Annu Rev Physiol. 1990;52:675-697. [PubMed] Willey RL, Bonifacino JS, Potts BJ, Martin MA, Klausner RD. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-9584. [PubMed] Yoshida T, Takao S, Kiyotani K, Sakaguchi T. Endoproteolytic activation of Newcastle disease virus fusion proteins requires an intracellular acidic environment. Virology. 1989 Jun;170(2):571-574. [PubMed
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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CaliforniaLyme
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posted
The Furin Inhibitor Hexa-d-Arginine Blocks the Activation of Pseudomonas aeruginosa Exotoxin A In Vivo
Sarac, M. Cameron, A. Lindberg, I. Infect Immun. 2002 December; 70(12): 7136-7139. doi: 10.1128/IAI.70.12.7136-7139.2002. Copyright � 2002, American Society for Microbiology The Furin Inhibitor Hexa-d-Arginine Blocks the Activation of Pseudomonas aeruginosa Exotoxin A In Vivo Miroslav S. Sarac, Angus Cameron,� and Iris Lindberg* Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112 *Corresponding author. Mailing address: Louisiana State University Health Sciences Center, Department of Biochemistry and Molecular Biology, 1901 Perdido St., New Orleans, LA 70112. Phone: (504) 568-4799. Fax: (504) 568-6598. E-mail: [email protected].
�Present address: Biochemistry Department, School of Medical Sciences, University of Bristol, Bristol, United Kingdom BS8 1TD. Received May 30, 2002; Revised August 6, 2002; Accepted August 20, 2002. This article has been cited by other articles in PMC. Abstract
The Pseudomonas aeruginosa exotoxin A (PEA) protein requires furin-mediated cleavage for manifestation of toxicity. We show here that the small stable furin inhibitor hexa-d-arginine amide effectively blocks PEA-induced cell lysis and is itself noncytotoxic. Administration of hexa-d-arginine to PEA-treated mice significantly improves their survival rate and also decreases circulating levels of tumor necrosis factor alpha.
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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CaliforniaLyme
Frequent Contributor (5K+ posts)
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1: Med Hypotheses. 2007;69(4):836-7. Epub 2007 Mar 21. Links
Consideration of acamprosate for treatment of amyotrophic lateral sclerosis.
Kast RE, Altschuler EL. Department of Psychiatry, University of Vermont, College of Medicine, 2 Church Street, Burlington, VT 05401, USA. [email protected]
Amyotrophic lateral sclerosis (ALS) is a fatal disease of degeneration of motor neurons. There is no known cure or life extending treatment.
Much recent work has suggested that a possible cause of ALS is constitutive opening of the calcium pore in glutamate sensitive AMPA channels secondary to a failure of RNA editing that would change a crucial glutamate in the channel to arginine.
Here, we point out that the small molecule pharmaceutical acamprosate, usually used as a drug to maintain alcohol abstinence, may block this calcium pore--as do the related molecules endogenous polyamines such as putrescine, cadaverine, spermidine and spermine--and thus might have use in ALS.
PMID: 17368956
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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I haven't researched ALS extensively, but what I have read mostly implicated glutamate in cell death. Looks like the calcium connection may be equally if not more important.
Also thought I had read somewhere that glutamate was also a factor with neuroborelliosis. A good reason to avoid MSG and the reason many Lymies can't tolerate glutamine supplements which can be very beneficial to heal gastrtis and other G.I. irritations.
I recently posted a journal article which stated that Bartonella required glutamine for growth.
These infections are all so entertwined it is mind boggling.
Bea Seibert
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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posted
I wonder if glutamate levels can be tested. I know I had an elevated pyruvate level.
Posts: 340 | From Ohio | Registered: Oct 2005
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