Knöferle, Johanna

[["dc.bibliographiccitation.firstpage","1350"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Cellular Biochemistry"],["dc.bibliographiccitation.lastpage","1361"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Scheller, C."],["dc.contributor.author","Knoferle, J."],["dc.contributor.author","Ullrich, A."],["dc.contributor.author","Prottengeier, J."],["dc.contributor.author","Racek, T."],["dc.contributor.author","Sopper, S."],["dc.contributor.author","Jassoy, C."],["dc.contributor.author","Rethwilm, A."],["dc.contributor.author","Koutsilieri, E."],["dc.date.accessioned","2018-11-07T09:58:54Z"],["dc.date.available","2018-11-07T09:58:54Z"],["dc.date.issued","2006"],["dc.description.abstract","CD95 (Fas/Apo-1) triggers apoptotic cell death via a caspase-dependent pathway. Inhibition of caspase activation blocks proapoptotic signaling and thus, prevents execution of apoptosis. Besides induction of apoptotic cell death, CD95 has been reported to trigger necrotic cell death in Susceptible cells. In this study, we investigated the interplay between apoptotic and necrotic cell death signaling in T cells. Using the agonistic CD95 antibody, 7C11, we found that caspase inhibition mediated by the pancaspase inhibitor, zVAD-fmk, prevented CD95-triggered cell death in Jurkat T cells but not in A3.01 Tcells, although typical hallmarks of apoptosis, such as DNA fragmentation or caspase activation were blocked. Moreover, the caspase-independent cell death in A3.01 cells exhibited typical signs of necrosis as detected by a rapid loss of cell membrane integrity and could be prevented by treatment with the radical scavenger butylated hydroxyanisole (BHA). Similar to CD95-induced cell death, apoptosis triggered by the DNA topoisomerase inhibitors, camptothecin or etoposide was shifted to necrosis when capsase activation was inhibited. In contrast to this, ZVAD was fully protective when apoptosis was triggered by the serpase inhibitor, N alpha-tosyl-phenyl-chlorotmethyl ketone (TPCK). TPCK was not protective when administered to anti-CD95/ZVAD-treated A3.01 cells, indicating that TPCK does not possess anti-necrotic activity but fails to activate the necrotic death pathway. Our findings show (a) that caspase inhibition does not always protect apoptotic T cells from dying but merely activates a caspase-independent mode of cell death that results in necrosis and (b) that the caspase-inhibitor-induced shift from apoptotic to necrotic cell death is dependent on the cell type and the proapoptotic stimulus."],["dc.identifier.doi","10.1002/jcb.20670"],["dc.identifier.isi","000236301500019"],["dc.identifier.pmid","16365881"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37468"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0730-2312"],["dc.title","Caspase inhibition in apoptotic T cells triggers necrotic cell death depending on the cell type and the proapoptotic stimulus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","81"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","93"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Gadjanski, Ivana"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Williams, Sarah K."],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Knöferle, Johanna"],["dc.contributor.author","Sättler, Muriel B."],["dc.contributor.author","Fairless, Richard"],["dc.contributor.author","Hochmeister, Sonja"],["dc.contributor.author","Sühs, Kurt-Wolfram"],["dc.contributor.author","Michaelis, Thomas"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Storch, Maria K."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2019-07-09T11:52:52Z"],["dc.date.available","2019-07-09T11:52:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Objective: The aim of this study was to investigate the role of voltage-dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis. Methods: Calcium ion (Ca2 ) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese-enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N-type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using -conotoxin GVIA, an N-type specific blocker. Results: We observed that pathological Ca2 influx into ONs during optic neuritis is mediated via N-type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of 1B, the pore-forming subunit of N-type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N-type VDCCs for inflammation-induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with -conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals. Interpretation: We conclude that N-type VDCCs play an important role in inflammation-induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca2 influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage."],["dc.identifier.doi","10.1002/ ana.21668"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60296"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Role of N-Type Voltage-Dependent Calcium Channels in Autoimmune Optic Neuritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1887"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Nature Protocols"],["dc.bibliographiccitation.lastpage","1896"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:43:17Z"],["dc.date.available","2017-09-07T11:43:17Z"],["dc.date.issued","2011"],["dc.description.abstract","In this protocol, we describe the imaging of single axons in the rat optic nerve in vivo. Axons are labeled through the intravitreal injection of adeno-associated viral vectors (AAVs) expressing a fluorophore (duration of the procedure similar to 1 h). Two weeks after intravitreal injection, the optic nerve is surgically exposed (duration similar to 1 h) and labeled axons are imaged with an epifluorescence microscope either for up to 8 h or repetitively on the following days. Additionally, intravitreal injection of calcium-sensitive dyes allows for imaging of intra-axonal calcium kinetics. This procedure enables the analysis of the morphological changes of degenerating axons in the optic nerve in different lesion paradigms, such as optic nerve crush, axotomy or pin lesion. Furthermore, the effects of pharmacological manipulations on axonal stability and axonal calcium kinetics in axons of the central nervous system can be studied in vivo."],["dc.identifier.doi","10.1038/nprot.2011.403"],["dc.identifier.gro","3142620"],["dc.identifier.isi","000298157100005"],["dc.identifier.pmid","22051801"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft (DFG)"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1754-2189"],["dc.title","Imaging of rat optic nerve axons in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","658"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Autophagy"],["dc.bibliographiccitation.lastpage","659"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Ostendorf, T."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:45:21Z"],["dc.date.available","2017-09-07T11:45:21Z"],["dc.date.issued","2010"],["dc.description.abstract","Axonal degeneration is a pathological hallmark of many traumatic and neurodegenerative neurological disorders. Although the underlying mechanisms remain largely unclear, increased autophagy and the influx of extracellular calcium have been implicated in the pathogenesis of axonal degeneration based on in vitro data. Using in vivo imaging of the rat optic nerve after crush lesion we could now show that both mechanisms are linked and play an important role in acute axonal degeneration in vivo. Our data suggest that crush lesion of the optic nerve induces a rapid calcium influx through calcium channels, which results in a secondary induction of autophagy that participates actively in axonal degradation. Therapeutic manipulation of both events could significantly alter the time course of acute axonal degeneration in vivo and may thus represent promising therapeutic targets for the future."],["dc.identifier.doi","10.4161/auto.6.5.12188"],["dc.identifier.gro","3142891"],["dc.identifier.isi","000279429200014"],["dc.identifier.pmid","20458173"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/344"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1554-8627"],["dc.title","Acute axonal degeneration in vivo is attenuated by inhibition of autophagy in a calcium-dependent manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6064"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","6069"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Ostendorf, T."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Planchamp, V."],["dc.contributor.author","Vutova, P."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Stadelmann, C."],["dc.contributor.author","Brück, W."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:07Z"],["dc.date.available","2017-09-07T11:46:07Z"],["dc.date.issued","2010"],["dc.description.abstract","Axonal degeneration is an initial key step in traumatic and neurodegenerative CNS disorders. We established a unique in vivo epifluorescence imaging paradigm to characterize very early events in axonal degeneration in the rat optic nerve. Single retinal ganglion cell axons were visualized by AAV-mediated expression of dsRed and this allowed the quantification of postlesional acute axonal degeneration (AAD). EM analysis revealed severe structural alterations of the cytoskeleton, cytoplasmatic vacuolization, and the appearance of autophagosomes within the first hours after lesion. Inhibition of autophagy resulted in an attenuation of acute axonal degeneration. Furthermore, a rapid increase of intraaxonal calcium levels following crush lesion could be visualized using a calcium-sensitive dye. Application of calcium channel inhibitors prevented crush-induced calcium increase and markedly attenuated axonal degeneration, whereas application of a calcium ionophore aggravated the degenerative phenotype. We finally demonstrate that increased postlesional autophagy is calcium dependent and thus mechanistically link autophagy and intraaxonal calcium levels. Both processes are proposed to be major targets for the manipulation of axonal degeneration in future therapeutic settings."],["dc.identifier.doi","10.1073/pnas.0909794107"],["dc.identifier.gro","3142949"],["dc.identifier.isi","000276159500067"],["dc.identifier.pmid","20231460"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/409"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","Mechanisms of acute axonal degeneration in the optic nerve in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","395"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","404"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Ramljak, S."],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Asif, A. R."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Wouters, F. S."],["dc.contributor.author","Heermann, S."],["dc.contributor.author","Krieglstein, K."],["dc.contributor.author","Zerr, I."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:02Z"],["dc.date.available","2017-09-07T11:46:02Z"],["dc.date.issued","2010"],["dc.description.abstract","Malfunction of the ubiquitin-proteasome system has been implicated as a causal factor in the pathogenesis of aggregation-related disorders, e.g. Parkinson's disease. We show here that Transforming growth factor-beta 1 (TGF-beta), a multifunctional cytokine and trophic factor for dopaminergic (DAergic) neurons modulates proteasome function in primary midbrain neurons. TGF-beta differentially inhibited proteasomal subactivities with a most pronounced time-dependent inhibition of the peptidyl-glutamyl peptide hydrolyzing-like and chymotrypsin-like subactivity. Regulation of proteasomal activity could be specifically quantified in the DAergic subpopulation. Protein blot analysis revealed an accumulation of ubiquitinated proteins after TGF-beta treatment. The identity of these enriched proteins was further analyzed by 2D-gel electrophoresis and mass spectrometry. We found epidermal fatty acid binding protein (EFABP) to be strongly increased and ubiquitinated after TGF-beta treatment and confirmed this finding by co-immunoprecipitation. While application of TGF-beta increased neurite regeneration in a scratch lesion model, downregulation of EFABP by siRNA significantly decreased this effect. We thus postulate that a differential regulation of proteasomal function, as demonstrated for TGF-beta, can result in an enrichment of proteins, such as EFABP, that mediate physiological functions, such as neurite regeneration. (C) 2010 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2010.02.011"],["dc.identifier.gro","3142916"],["dc.identifier.isi","000277648200010"],["dc.identifier.pmid","20211260"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/373"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: DFG-Research Center for Molecular Physiology of the Brain"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1095-953X"],["dc.relation.issn","0969-9961"],["dc.title","TGF-beta 1 enhances neurite outgrowth via regulation of proteasome function and EFABP"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]