Ramljak, Sanja

[["dc.bibliographiccitation.firstpage","5370"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Proteome Research"],["dc.bibliographiccitation.lastpage","5382"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Schumacher, Julia"],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Schaffrath, Michael"],["dc.contributor.author","Zischler, Hans"],["dc.contributor.author","Herlyn, Holger"],["dc.date.accessioned","2018-11-07T09:17:03Z"],["dc.date.available","2018-11-07T09:17:03Z"],["dc.date.issued","2013"],["dc.description.abstract","We investigated possible associations between sequence evolution of mammalian sperm proteins and their phosphorylation status in humans. As a reference, spermatozoa from three normozoospermic men were analyzed combining two-dimensional gel electrophoresis, immuno-blotting, and mass spectrometry. We identified 99 sperm proteins (thereof 42 newly described) and determined the phosphorylation status for most of them. Sequence evolution was studied across six mammalian species using nonsynonymous/synonymous rate ratios (dN/dS) and amino acid distances. Site-specific purifying selection was assessed employing average ratios of evolutionary rates at phosphorylated versus nonphosphorylated amino acids (a). According to our data, mammalian sperm proteins do not show statistically significant sequence conservation difference, no matter if the human ortholog is a phosphoprotein with or without tyrosine (Y) phosphorylation. In contrast, overall phosphorylation of human sperm proteins, i.e., phosphorylation at serine (S), threonine (T), and/or Y residues, associates with above-average conservation of sequences. Complementary investigations suggest that numerous protein-protein interactants constrain sequence evolution of sperm phosphoproteins. Although our findings reject a special relevance of Y phosphorylation for sperm functioning, they still indicate that overall phosphorylation substantially contributes to proper functioning of sperm proteins. Hence, phosphorylated sperm proteins might be considered as prime candidates for diagnosis and treatment of reduced male fertility."],["dc.identifier.doi","10.1021/pr400228c"],["dc.identifier.isi","000328231300003"],["dc.identifier.pmid","23919900"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28074"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","1535-3907"],["dc.relation.issn","1535-3893"],["dc.title","Evolutionary Conservation of Mammalian Sperm Proteins Associates with Overall, not Tyrosine, Phosphorylation in Human Spermatozoa"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","129"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Protein Expression and Purification"],["dc.bibliographiccitation.lastpage","136"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Heinig, Lars"],["dc.contributor.author","Mueller, Daniel A."],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Holznagel, Edgar"],["dc.contributor.author","Stuke, Andreas W."],["dc.date.accessioned","2022-10-06T13:33:22Z"],["dc.date.available","2022-10-06T13:33:22Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/j.pep.2009.09.015"],["dc.identifier.pii","S104659280900240X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/115615"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.issn","1046-5928"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.title","Inducible expression of chimpanzee prion protein (PrP) in murine PrP knock-out cells"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","463"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","HYBRIDOMA"],["dc.bibliographiccitation.lastpage","472"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Mueller, Daniel A."],["dc.contributor.author","Heinig, Lars"],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Krueger, Astrid"],["dc.contributor.author","Schulte, Reiner"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Stuke, Andreas W."],["dc.date.accessioned","2018-11-07T08:36:15Z"],["dc.date.available","2018-11-07T08:36:15Z"],["dc.date.issued","2010"],["dc.description.abstract","Because of their high antigen specificity and metabolic stability, genetically engineered human monoclonal antibodies are on the way to becoming one of the most promising medical diagnostics and therapeutics. In order to establish an in vitro system capable of producing such biosimilar antibodies, we used human constant chain sequences to design the novel human antibody expressing vector cassette pMAB-ABX. A bidirectional tetracycline (tet)-controllable promotor was used for harmonized expression of immunoglobulin type G (IgG) heavy and light chains. As an example we used anti-prion protein (anti-PrP) IgGs. Therefore, the variable heavy (V(H)) and light chain (V(L)) sequences of anti-PrP antibodies, previously generated in our laboratory by DNA immunization of prion protein knock-out mice, were isolated from murine hybridoma cell lines and inserted into pMAB-ABX vector. After transfection of Chinese hamster ovary (CHO) cells, a number of stable antibody producing cell clones were selected. One cell line (pMAB-ABX-13F10/3B5) stably expressing the recombinant humanized antibody (rechuAb) 13F10/3B5 was selected for detailed characterization by Western blot, immunofluorescence, and flow cytometric analyses. The full-length recombinant humanized IgG antibody showed a high level of expression in the cytoplasm. In conclusion, the new cell system described here is a suitable tool to produce functional intact full-length humanized IgG antibodies."],["dc.description.sponsorship","DPZ; Ersatzmethoden zum Tierversuch; German BMBF [FKZ 0315279A]"],["dc.identifier.doi","10.1089/hyb.2010.0041"],["dc.identifier.isi","000285145300001"],["dc.identifier.pmid","21087094"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18267"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mary Ann Liebert Inc"],["dc.relation.issn","1554-0014"],["dc.title","Conditional Expression of Full-Length Humanized Anti-Prion Protein Antibodies in Chinese Hamster Ovary Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1640"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","1650"],["dc.bibliographiccitation.volume","169"],["dc.contributor.author","Weiss, Elisabeth"],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Asif, Abdul Rahman"],["dc.contributor.author","Ciesielczyk, Barbara"],["dc.contributor.author","Schmitz, M."],["dc.contributor.author","Gawinecka, Joanna"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Behrens, C."],["dc.contributor.author","Zerr, I."],["dc.date.accessioned","2018-11-07T08:39:11Z"],["dc.date.available","2018-11-07T08:39:11Z"],["dc.date.issued","2010"],["dc.description.abstract","The definite physiological role of the cellular prion protein (PrPc) remains elusive. There is ample in vitro and in vivo evidence suggesting a neuroprotective role for PrPc. On the other hand, several in vitro and in vivo studies demonstrated detrimental effects of PrPc overexpression through activation of a p53 pathway. Recently, we reported that transient overexpression of PrPc in human embryonic kidney 293 cells elicits proteome expression changes which point to deregulation of proteins involved in energy metabolism and cellular homeostasis. Here we report proteome expression changes following stable PrPc overexpression in human neuronal SH-SY5Y cells. In total 18 proteins that are involved in diverse biological processes were identified as differentially regulated. The majority of these proteins is involved in cell signaling, cytoskeletal organization and protein folding. Annexin V exhibited a several fold up-regulation following stable PrPc overexpression in SH-SY5Y cells. This finding has been reproduced in alternative, mouse N2a and human SK-N-LO neuroblastoma cell lines transiently overexpressing PrPc. Annexin V plays an important role in maintenance of calcium homeostasis which when disturbed can activate a p53-dependent cell death. Although we did not detect changes in p53 expression between PrPc overexpressing SH-SY5Y and control cells, deregulation of several proteins including annexin V, polyglutamine tract-binding protein-1, spermine synthase and transgelin 2 indicates disrupted cellular equilibrium. We conclude that stable PrPc overexpression in SH-SY5Y cells is sufficient to perturb cellular balance but insufficient to affect p53 expression. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neuroscience.2010.06.013"],["dc.identifier.isi","000281050600016"],["dc.identifier.pmid","20547212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18932"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0306-4522"],["dc.title","CELLULAR PRION PROTEIN OVEREXPRESSION DISTURBS CELLULAR HOMEOSTASIS IN SH-SY5Y NEUROBLASTOMA CELLS BUT DOES NOT ALTER p53 EXPRESSION: A PROTEOMIC STUDY"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2681"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of Proteome Research"],["dc.bibliographiccitation.lastpage","2695"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Groschup, Martin H."],["dc.contributor.author","Buschman, Anne"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Bodemer, Walter"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T11:13:39Z"],["dc.date.available","2018-11-07T11:13:39Z"],["dc.date.issued","2008"],["dc.description.abstract","The physiological role of the cellular prion protein (PrPc) is still not fully understood. Current evidence strongly suggests that PrPc overexpression in different cell lines sensitizes cells to apoptotic stimuli through a p53 dependent pathway. On the other hand, an expression of PrPc in PrPc-deficient cells undergoing apoptosis exhibited repeatedly antiapoptotic effects. Therefore, the presence/absence and/ or the level of PrPc expression seem to be critical for the fluctuation between PrPc's pro- and antiapoptotic properties. The present study examined whether an overexpression of PrPc itself, without addition of any apoptotic agent, can lead to proteome changes that might account for the higher responsiveness to apoptotic stimuli. Beyond this, we examined whether the sole introduction of PrPc into PrPc-deficient cells could be sufficient to up-regulate antiapoptotic proteins capable of mitigating apoptosis. For this purpose, we used two cell lines, one expressing [human embryonic kidney (HEK) 293 cells] and the other lacking (mouse neuronal PrPc-deficient cells) endogenous PrPc. Protein profiling following transient PrPc overexpression in HEK 293 cells revealed a major PrPc involvement in regulation of proteins participating in energy metabolism and cellular homeostasis, whereas transient introduction of PrPc into mouse neuronal PrPc-deficient cells resulted mainly in the regulation of proteins involved in protection against oxidative stress and apoptosis. In addition, we report for the first time that PrPc overexpression influenced the regulation of several proteins known to have contributory roles in the pathogenesis of Alzheimer disease (AD). Revealing the correlation between presence/absence and/or different levels of PrPc expression with the regulation of certain cellular proteins might further contribute to our understanding of the complex role of PrPc in cell physiology."],["dc.identifier.doi","10.1021/pr7007187"],["dc.identifier.isi","000257449500009"],["dc.identifier.pmid","18537284"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53946"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","1535-3893"],["dc.title","Physiological role of the cellular prion protein (PrPc): Protein profiling study in two cell culture systems"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","155"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","167"],["dc.bibliographiccitation.volume","271"],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Schenkel, Sara"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Carimalo, Julie"],["dc.contributor.author","Doeppner, Thorsten R."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Weise, Jens"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T09:52:13Z"],["dc.date.available","2018-11-07T09:52:13Z"],["dc.date.issued","2015"],["dc.description.abstract","Although a physiological function of the cellular prion protein (PrPc) is still not fully clarified, a PrPc-mediated neuroprotection against hypoxic/ischemic insult is intriguing. After ischemic stroke prion protein knockout mice (Prnp(0/0)) display significantly greater lesions as compared to wild-type (WT) mice. Earlier reports suggested an interaction between the glycolytic enzyme lactate dehydrogenase (LDH) and PrPc. Since hypoxic environment enhances LDH expression levels and compels neurons to rely on lactate as an additional oxidative substrate for energy metabolism, we examined possible differences in LDH protein expression in WT and Prnp(0/0) knockout models under normoxic/hypoxic conditions in vitro and in vivo, as well as in a HEK293 cell line. While no differences are observed under normoxic conditions, LDH expression is markedly increased after 60-min and 90-min of hypoxia in WT vs. Prnp(0/0) primary cortical neurons with concurrent less hypoxia-induced damage in the former group. Likewise, cerebral ischemia significantly increases LDH levels in WT vs. Prnp(0/0) mice with accompanying smaller lesions in the WT group. HEK293 cells overexpressing PrPc show significantly higher LDH expression/activity following 90-min of hypoxia as compared to control cells. Moreover, a cytoplasmic co-localization of LDH and PrPc was recorded under both normoxic and hypoxic conditions. Interestingly, an expression of monocarboxylate transporter 1, responsible for cellular lactate uptake, increases with PrPc-overexpression under normoxic conditions. Our data suggest LDH as a direct PrPc interactor with possible physiological relevance under low oxygen conditions. (C) 2015 Published by Elsevier Inc."],["dc.identifier.doi","10.1016/j.expneurol.2015.04.025"],["dc.identifier.isi","000362627200017"],["dc.identifier.pmid","26024859"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36070"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1090-2430"],["dc.relation.issn","0014-4886"],["dc.title","Cellular prion protein directly interacts with and enhances lactate dehydrogenase expression under hypoxic conditions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]