Khan, Niamat

[["dc.bibliographiccitation.firstpage","6694"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Molecules"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Khan, Niamat"],["dc.contributor.author","Shahid, Sidra"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2021-12-01T09:22:52Z"],["dc.date.available","2021-12-01T09:22:52Z"],["dc.date.issued","2021"],["dc.description.abstract","Chromatin is a dynamic structure comprising of DNA and proteins. Its unique nature not only help to pack the DNA tightly within the cell but also is pivotal in regulating gene expression DNA replication. Furthermore it also protects the DNA from being damaged. Various proteins are involved in making a specific complex within a chromatin and the knowledge about these interacting partners is helpful to enhance our understanding about the pathophysiology of various chromatin associated diseases. Moreover, it could also help us to identify new drug targets and design more effective remedies. Due to the existence of chromatin in different forms under various physiological conditions it is hard to develop a single strategy to study chromatin associated proteins under all conditions. In our current review, we tried to provide an overview and comparative analysis of the strategies currently adopted to capture the DNA bounded protein complexes and their mass spectrometric identification and quantification. Precise information about the protein partners and their function in the DNA-protein complexes is crucial to design new and more effective therapeutic molecules against chromatin associated diseases."],["dc.description.abstract","Chromatin is a dynamic structure comprising of DNA and proteins. Its unique nature not only help to pack the DNA tightly within the cell but also is pivotal in regulating gene expression DNA replication. Furthermore it also protects the DNA from being damaged. Various proteins are involved in making a specific complex within a chromatin and the knowledge about these interacting partners is helpful to enhance our understanding about the pathophysiology of various chromatin associated diseases. Moreover, it could also help us to identify new drug targets and design more effective remedies. Due to the existence of chromatin in different forms under various physiological conditions it is hard to develop a single strategy to study chromatin associated proteins under all conditions. In our current review, we tried to provide an overview and comparative analysis of the strategies currently adopted to capture the DNA bounded protein complexes and their mass spectrometric identification and quantification. Precise information about the protein partners and their function in the DNA-protein complexes is crucial to design new and more effective therapeutic molecules against chromatin associated diseases."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/molecules26216694"],["dc.identifier.pii","molecules26216694"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94502"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1420-3049"],["dc.relation.orgunit","Institut für Klinische Chemie"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Current Analytical Strategies in Studying Chromatin-Associated-Proteome (Chromatome)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","219843"],["dc.bibliographiccitation.journal","Mediators of Inflammation"],["dc.contributor.author","Khan, Niamat"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2018-11-07T10:03:23Z"],["dc.date.available","2018-11-07T10:03:23Z"],["dc.date.issued","2015"],["dc.description.abstract","Human gastrointestinal tract is covered by a monolayer of specialized epithelial cells that constitute a protective barrier surface to external toxic and infectious agents along with metabolic and digestive functions. Intercellular junctions, among epithelial cells, such as desmosomes, adherens, gap, and tight junctions (TJs), not only provide mechanical integrity but also limit movement of molecules across the monolayer. TJ is a complex structure composed of approximately 35 different proteins that interact with each other at the apical side of two adjacent epithelial cells. Claudin family proteins are important members of TJ with so far 24 known isoforms in different species. Claudins are structural proteins of TJ that help to control the paracellular movement by forming fence and barrier across the epithelial monolayer. Altered function of claudins is implicated in different form of cancers, inflammatory bowel diseases (IBDs), and leaky diarrhea. Based on their significant role in the molecular architecture of TJ, diversity, and disease association, further understanding about claudin family proteins and their genetic/epigenetic regulators is indispensable."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1155/2015/219843"],["dc.identifier.isi","000353129100001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11393"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38449"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Hindawi Publishing Corp"],["dc.relation.issn","1466-1861"],["dc.relation.issn","0962-9351"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Transcriptional Regulators of Claudins in Epithelial Tight Junctions"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","381"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","6"],["dc.contributor.affiliation","Khan, Niamat; 1Proteomics Group, Institute for Clinical Chemistry/UMG-Laboratories, University Medical Centre Goettingen, Germany"],["dc.contributor.affiliation","Pantakani, D. V. Krishna; 1Proteomics Group, Institute for Clinical Chemistry/UMG-Laboratories, University Medical Centre Goettingen, Germany"],["dc.contributor.affiliation","Binder, Lutz; 1Proteomics Group, Institute for Clinical Chemistry/UMG-Laboratories, University Medical Centre Goettingen, Germany"],["dc.contributor.affiliation","Qasim, Muhammad; 1Proteomics Group, Institute for Clinical Chemistry/UMG-Laboratories, University Medical Centre Goettingen, Germany"],["dc.contributor.affiliation","Asif, Abdul R.; 1Proteomics Group, Institute for Clinical Chemistry/UMG-Laboratories, University Medical Centre Goettingen, Germany"],["dc.contributor.author","Khan, Niamat"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Qasim, Muhammad"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2018-11-07T09:47:23Z"],["dc.date.available","2018-11-07T09:47:23Z"],["dc.date.issued","2015"],["dc.date.updated","2022-09-05T18:24:21Z"],["dc.description.abstract","Background: Mycophenolic acid (MPA) is an important immunosuppressive drug (ISD) prescribed to prevent graft rejection in the organ transplanted patients, however, its use is also associated with adverse side effects like sporadic gastrointestinal (GI) disturbances. Recently, we reported the MPA induced tight junctions (TJs) deregulation which involves MLCK/MLC-2 pathway. Here, we investigated the global histone acetylation as well as gene specific chromatin signature of several genes associated with TJs regulation in Caco-2 cells after MPA treatment. Results : The epigenetic analysis shows that MPA treatment increases the global histone acetylation levels as well as the enrichment for transcriptional active histone modification mark (H3K4me3) at promoter regions of p38MAPK, ATF-2, MLCK, and MLC-2. In contrast, the promoter region of occludin was enriched for transcriptional repressive histone modification mark (H3K27me3) after MPA treatment. In line with the chromatin status, MPA treatment increased the expression of p38MAPK, ATF-2, MLCK, and MLC-2 both at transcriptional and translational level, while occludin expression was negatively influenced. Interestingly, the MPA induced gene expression changes and functional properties of Caco-2 cells could be blocked by the inhibition of p38MAPK using a chemical inhibitor (SB203580). Conclusions : Collectively, our results highlight that MPA disrupts the structure of TJs via p38MAPK-dependent activation of MLCK/MLC-2 pathway that results in decreased integrity of Caco-2 monolayer. These results led us to suggest that p38MAPK-mediated lose integrity of epithelial monolayer could be the possible cause of GI disturbance (barrier dysfunction) in the intestine, leading to leaky style diarrhea observed in the organ transplanted patients treated with MPA."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.3389/fphys.2015.00381"],["dc.identifier.isi","000366891500001"],["dc.identifier.pmid","26733876"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12763"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35100"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.relation.issn","1664-042X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Immunosuppressant MPA Modulates Tight Junction through Epigenetic Activation of MLCK/MLC-2 Pathway via p38MAPK"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","597"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Khan, Niamat"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2018-11-07T10:16:02Z"],["dc.date.available","2018-11-07T10:16:02Z"],["dc.date.issued","2016"],["dc.description.abstract","Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system. This study investigates whether MPA induces epigenetic changes which lead to GI complications, especially diarrhea. Methods: We employed a Chromatin Immunoprecipitation-O-Proteomics (ChIP-O-Proteomics) approach to identify proteins associated with active (H3K4me3) as well as repressive (H3K27me3) chromatin histone modifications in MPA-treated cells, and further characterized the role of midkine, a H3K4me3-associated protein, in the context of epithelial monolayer permeability. Results: We identified a total of 333 and 306 proteins associated with active and repressive histone modification marks, respectively. Among them, 241 proteins were common both in active and repressive chromatin, 92 proteins were associated exclusively with the active histone modification mark, while 65 proteins remained specific to repressive chromatin. Our results show that 45 proteins which bind to the active and seven proteins which bind to the repressive chromatin region exhibited significantly altered abundance in MPA-treated cells as compared to DMSO control cells. A number of novel proteins whose function is not known in bowel barrier regulation were among the identified proteins, including midkine. Our functional integrity assays on the Caco-2 cell monolayer showed that the inhibition of midkine expression prior to MPA treatment could completely block the MPA-mediated increase in barrier permeability. Conclusions: The ChIP-O-Proteomics approach delivered a number of novel proteins with potential implications in MPA toxicity. Consequently, it can be proposed that midkine inhibition could be a potent therapeutic approach to prevent the MPA-mediated increase in TJ permeability and leak flux diarrhea in organ transplant patients."],["dc.description.sponsorship","Open-Access Publikationsfonds 2016"],["dc.identifier.doi","10.3390/ijms17040597"],["dc.identifier.isi","000374585300174"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13238"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40951"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","438"],["dc.bibliographiccitation.journal","Frontiers in physiology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.affiliation","Khan, Niamat; 1Institute for Clinical Chemistry/UMG-Laboratories, University Medical Center Goettingen, Germany"],["dc.contributor.affiliation","Binder, Lutz; 1Institute for Clinical Chemistry/UMG-Laboratories, University Medical Center Goettingen, Germany"],["dc.contributor.affiliation","Pantakani, D. V. Krishna; 1Institute for Clinical Chemistry/UMG-Laboratories, University Medical Center Goettingen, Germany"],["dc.contributor.affiliation","Asif, Abdul R.; 1Institute for Clinical Chemistry/UMG-Laboratories, University Medical Center Goettingen, Germany"],["dc.contributor.author","Khan, Niamat"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Pantakani, D. V. Krishna"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2019-07-09T11:43:35Z"],["dc.date.available","2019-07-09T11:43:35Z"],["dc.date.issued","2017"],["dc.date.updated","2022-09-05T20:55:41Z"],["dc.description.abstract","Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ transplanted patients. However, its use is sporadically linked to leak flux diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients through yet unknown mechanisms. Recently, we identified Midkine as a modulator of tight junctions (TJs) permeability in MPA treated Caco-2 monolayer. In the present study, we investigated the possible involvement of Midkine dependent PI3K pathway in alteration of TJs under MPA treatment. Caco-2 cells were grown as monolayer to develop TJs and were treated for 72 h with DMSO (control) or MPA in presence and absence of Midkine inhibitor (iMDK) or PI3K inhibitors (LY/AMG). Caco-2 monolayer integrity was assessed by transepithelial electrical resistance (TEER) and FITC-dextran assays. Our functional assays showed that PI3K inhibitors (LY/AMG) can significantly inhibit the compromised TJs integrity of MPA-treated Caco-2 cells monolayer. Chromatin immunoprecipitation analyses showed a significant epigenetic activation of Midkine, PI3K, Cdx-2, and Cldn-2 genes and epigenetic repression of Cldn-1 gene after MPA treatment. The MPA-induced epigenetic alterations were further confirmed by mRNA and protein expression analysis. Collectively, our data shows that PI3K pathway as the downstream target of Midkine which in turn modulates p38MAPK and pAKT signaling to alter TJs permeability in Caco-2 cell monolayers treated with MPA. These results highlight the possible use of either Midkine or PI3K inhibitors as therapeutic agents to prevent MPA induced GI disturbances."],["dc.identifier.doi","10.3389/fphys.2017.00438"],["dc.identifier.pmid","28694783"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14582"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58920"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.relation.issn","1664-042X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]