Nau, Roland

[["dc.bibliographiccitation.artnumber","64"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Jaiswal, Manoj Kumar"],["dc.contributor.author","Zech, Wolf-Dieter"],["dc.contributor.author","Goos, Miriam"],["dc.contributor.author","Leutbecher, Christine"],["dc.contributor.author","Ferri, Alberto"],["dc.contributor.author","Zippelius, Annette"],["dc.contributor.author","Carri, Maria Teresa"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Keller, Bernhard U."],["dc.date.accessioned","2018-11-07T08:28:40Z"],["dc.date.available","2018-11-07T08:28:40Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN) in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD) imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results: To gain insights into the molecular mechanisms of SOD1(G93A) associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage - dependent cytosolic Ca(2+) elevations and mitochondria - controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca(2+) elevations in WT (SH-SY5Y(WT)) and G93A (SH-SY5Y(G93A)) expressing cells were observed. In contrast, mitochondrial intracellular Ca(2+) release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca(2+) regulation. Conclusion: In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca(2+)]i and [Ca(2+)](mito) measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells an established cellular model of ALS. The primary goals of this paper are (1) method development, and (2) screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca(2+)-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS."],["dc.identifier.doi","10.1186/1471-2202-10-64"],["dc.identifier.isi","000268695200001"],["dc.identifier.pmid","19545440"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5754"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16476"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","1471-2202"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","131"],["dc.bibliographiccitation.journal","BMC infectious diseases"],["dc.bibliographiccitation.lastpage","12"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Goos, Miriam"],["dc.contributor.author","Zech, Wolf-Dieter"],["dc.contributor.author","Jaiswal, Manoj Kumar"],["dc.contributor.author","Balakrishnan, Saju"],["dc.contributor.author","Ebert, Sandra"],["dc.contributor.author","Mitchell, Timothy"],["dc.contributor.author","Carrì, Maria Teresa"],["dc.contributor.author","Keller, Bernhard U."],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2019-07-10T08:13:02Z"],["dc.date.available","2019-07-10T08:13:02Z"],["dc.date.issued","2007"],["dc.description.abstract","Background: Infections can aggravate the course of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in the anti-oxidant enzyme Cu,Zn superoxide dismutase (EC 1.15.1.1, SOD1) are associated with familial ALS. Streptococcus pneumoniae, the most frequent respiratory pathogen, causes damage by the action of the cholesterol-binding virulence factor pneumolysin and by stimulation of the innate immune system, particularly via Toll-like-receptor 2. Methods: SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) and SH-SY5Y neuroblastoma cells ...Results: SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) were more vulnerable to the neurotoxic action of pneumolysin and to the attack of monocytes stimulated by Pam3CSK4 than SH-SY5Y cells transfected with wild-type human SOD1. The enhanced pneumolysin toxicity in G93A-SOD1 neuronal cells depended on the inability of these cells to cope with an increased calcium influx caused by pores formed by pneumolysin ...Conclusion: The particular vulnerability of G93A-SOD1 neuronal cells to hemolysins and inflammation may be partly responsible for the clinical deterioration of ALS patients during infections. These findings link infection and motor neuron disease and suggest early treatment of respiratory infections in ALS patients."],["dc.identifier.fs","194629"],["dc.identifier.ppn","559657781"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61105"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","616"],["dc.title","Expression of a Cu,Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of neuroblastoma cells to infectious injury"],["dc.title.alternative","Research article"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]