Ahmad, Shakil

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Knierim, Maria"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2020-12-10T14:10:25Z"],["dc.date.available","2020-12-10T14:10:25Z"],["dc.date.issued","2020"],["dc.description.abstract","Pharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias."],["dc.identifier.doi","10.1007/s00395-020-0780-8"],["dc.identifier.pmid","32078054"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70756"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/349"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","179"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Current Heart Failure Reports"],["dc.bibliographiccitation.lastpage","186"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-01-30T13:29:01Z"],["dc.date.available","2019-01-30T13:29:01Z"],["dc.date.issued","2017"],["dc.description.abstract","Over the last years, evidence is accumulating that enhanced late sodium current (INaL) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of INaL-induced arrhythmias and the significance of INaL-inhibition as a possible therapeutic approach."],["dc.identifier.doi","10.1007/s11897-017-0333-0"],["dc.identifier.pmid","28455610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57422"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1546-9549"],["dc.title","Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","687"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nature Cell Biology"],["dc.bibliographiccitation.lastpage","699"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Gao, Xuefei"],["dc.contributor.author","Nowak-Imialek, Monika"],["dc.contributor.author","Chen, Xi"],["dc.contributor.author","Chen, Dongsheng"],["dc.contributor.author","Herrmann, Doris"],["dc.contributor.author","Ruan, Degong"],["dc.contributor.author","Chen, Andy Chun Hang"],["dc.contributor.author","Eckersley-Maslin, Melanie A."],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Lee, Yin Lau"],["dc.contributor.author","Liu, Pentao"],["dc.date.accessioned","2022-10-06T13:34:15Z"],["dc.date.available","2022-10-06T13:34:15Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41556-019-0333-2"],["dc.identifier.pii","333"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/115866"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1476-4679"],["dc.relation.issn","1465-7392"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","http://www.springer.com/tdm"],["dc.title","Establishment of porcine and human expanded potential stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","321"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Radiation and Environmental Biophysics"],["dc.bibliographiccitation.lastpage","338"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Moriconi, Federico"],["dc.date.accessioned","2018-11-07T09:22:03Z"],["dc.date.available","2018-11-07T09:22:03Z"],["dc.date.issued","2013"],["dc.description.abstract","The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far. Rats were exposed to selective liver FI (total dose 60 Gy, 2 Gy/day) or HDI (25 Gy) and were killed three months after the end of irradiation. To study acute effects, HDI-treated rats were additionally killed at several time points between 1 and 48 h. Three months after irradiation, no differences between FI and HDI treatment were found for macroscopically detectable small \"scars\" on the liver surface and for an increased number of neutrophil granulocytes distributed in the portal fields and through the liver parenchyma. As well, no changes in HE-stained tissues or clear signs of fibrosis were found around the portal vessels. Differences were seen for the number of bile ducts being increased in FI- but not in HDI-treated livers. Serum levels indicative of liver damage were determined for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gamma GT) and lactate dehydrogenase (LDH). A significant increase of AP was detected only after FI while HDI led to the significant increases of AST and LDH serum levels. By performing RT-PCR, we detected up-regulation of matrix metalloproteinases, MMP-2, MMP-9, MMP-14, and of their inhibitors, TIMP-1, TIMP-2 and TIMP-3, shortly after HDI, but not at 3 month after FI or HDI. Overall, we saw punctual differences after FI and HDI, and a diffuse formation of small scars at the liver surface. Lack of \"provisional clot\"-formation and absence of recruitment of mononuclear phagocytes could be one explanation for scar formation as incomplete repair response to irradiation."],["dc.identifier.doi","10.1007/s00411-013-0468-7"],["dc.identifier.isi","000322033000004"],["dc.identifier.pmid","23595725"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29250"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0301-634X"],["dc.title","Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1807"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","1821"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Alwahsh, Salamah Mohammad"],["dc.contributor.author","Xu, Min"],["dc.contributor.author","Seyhan, Hatice Ali"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Schultze, Frank Christian"],["dc.date.accessioned","2018-11-07T09:43:39Z"],["dc.date.available","2018-11-07T09:43:39Z"],["dc.date.issued","2014"],["dc.description.abstract","AIM: To explore lipocalin-2 (LCN-2) expression and its possible role and mechanism(s) of production in rat models of diet-inducible fatty liver. METHODS: Fatty liver was triggered in male Sprague-Dawley rats fed either with liquid Lieber-DeCarli (LDC) or LDC + 70% cal fructose (L-HFr) diet for 4 or 8 wk. Chow-nourished animals served as controls. Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting. Serum LCN-2, fasting leptin, and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay, Radioimmunoassay, and colorimetric assays, respectively. The localization of LCN-2 in the liver was detected by using immunofluorescence staining. Furthermore, HE stain was used to evaluate hepatic fat degeneration and inflammation. RESULTS: Both LDC-fed and L-HFr-fed rat histologically featured fatty liver. In the liver, mRNA transcriptions of Mcp-1, a2-m, Il-8 and Glut5 were increased in the L-HFr group at both time points (P < 0.001), while the transcription of Tlr4, Inos, and Tnf-alpha was significantly up-regulated at week 4. Interestingly, hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control (P < 0.001). In contrast to HDL-cholesterol, systemic levels of LCN-2, fasting leptin and triglycerides were elevated in the L-HFr regimen (P < 0.001). Moreover, protein expression of hepatic LCN-2, CD14, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal was increased in the L-HFr group. Conversely, the hepatic expression of PGC-1 alpha (a mitochondrial-biogenic protein) was reduced in the L-HFr category at week 8. The localization of LCN-2 in the liver was predominantly restricted to MPO+ granulocytes. CONCLUSION: Fructose diet up-regulates hepatic LCN-2 expression, which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction. The LCN-2 may be involved in liver protection. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved."],["dc.description.sponsorship","Open Access Publikationsfonds 2014"],["dc.identifier.doi","10.3748/wjg.v20.i7.1807"],["dc.identifier.isi","000331966100016"],["dc.identifier.pmid","24587658"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34228"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Baishideng Publ Grp Co Ltd"],["dc.relation.issn","2219-2840"],["dc.relation.issn","1007-9327"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver"],["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","6586"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Hartmann, Nico Horst"],["dc.contributor.author","A. Mohamed, Belal"],["dc.contributor.author","Krekeler, Miriam Celine"],["dc.contributor.author","Maurer, Wiebke"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Trum, Maximilian"],["dc.contributor.author","Sossalla, Samuel Tobias"],["dc.date.accessioned","2021-12-01T09:20:52Z"],["dc.date.available","2021-12-01T09:20:52Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract An interplay between Ca 2+ /calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na + current (I NaL ) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform Na V 1.8 for CaMKIIδc-dependent proarrhythmia. In a CRISPR-Cas9-generated human iPSC-cardiomyocyte homozygous knock-out of Na V 1.8, we demonstrate that Na V 1.8 contributes to I NaL formation. In addition, we reveal a direct interaction between Na V 1.8 and CaMKIIδc in cardiomyocytes isolated from patients with heart failure (HF). Using specific blockers of Na V 1.8 and CaMKIIδc, we show that Na V 1.8-driven I NaL is CaMKIIδc-dependent and that Na V 1.8-inhibtion reduces diastolic SR-Ca 2+ leak in human failing cardiomyocytes. Moreover, increased mortality of CaMKIIδc-overexpressing HF mice is reduced when a Na V 1.8 knock-out is introduced. Cellular and in vivo experiments reveal reduced ventricular arrhythmias without changes in HF progression. Our work therefore identifies a proarrhythmic CaMKIIδc downstream target which may constitute a prognostic and antiarrhythmic strategy."],["dc.identifier.doi","10.1038/s41467-021-26690-1"],["dc.identifier.pii","26690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94290"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/412"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","Detrimental proarrhythmogenic interaction of Ca2+/calmodulin-dependent protein kinase II and NaV1.8 in heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","337"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Shock"],["dc.bibliographiccitation.lastpage","345"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Ahmad, Ghayyor"],["dc.contributor.author","Alwahsh, Salamah Mohammad"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:41:37Z"],["dc.date.available","2018-11-07T09:41:37Z"],["dc.date.issued","2014"],["dc.description.abstract","Decreased serum and increased hepatic iron uptake is the hallmark of acute-phase (AP) response. Iron uptake is controlled by iron transport proteins such as transferrin receptors (TfRs) and lipocalin 2 (LCN-2). The current study aimed to understand the regulation of iron uptake in primary culture hepatocytes in the presence/absence of AP mediators. Rat hepatocytes were stimulated with different concentrations of iron alone (0.01, 0.1, 0.5 mM) and AP cytokines (interleukin 6 [IL-6], IL-1, tumor necrosis factor ) in the presence/absence of iron (FeCl3: 0.1 mM). Hepatocytes were harvested at different time points (0, 6, 12, 24 h). Total mRNA and proteins were extracted for reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. A significant iron uptake was detected with 0.1 mM iron administration with a maximum (133.37 +/- 4.82 mu g/g of protein) at 24 h compared with control and other iron concentrations. This uptake was further enhanced in the presence of AP cytokines with a maximum iron uptake (481 +/- 25.81 mu g/g of protein) after concomitant administration of IL-6 + iron to cultured hepatocytes. Concomitantly, gene expression of LCN-2 and ferritin subunits (light- and heavy-chain ferritin subunits) was upregulated by iron or/and AP cytokines with a maximum at 24 h both at mRNA and protein levels. In contrast, a decreased TfR1 level was detected by IL-6 and iron alone, whereas combination of iron and AP cytokines (mainly IL-6) abrogated the downregulation of TfR1. An increase in LCN-2 release into the supernatant of cultured hepatocytes was observed after addition of iron/AP cytokines into the medium. This increase in secretion was further enhanced by combination of IL-6 + iron. In conclusion, iron uptake is tightly controlled by already present iron concentration in the culture. This uptake can be further enhanced by AP cytokines, mainly by IL-6."],["dc.identifier.doi","10.1097/SHK.0000000000000107"],["dc.identifier.isi","000335648600011"],["dc.identifier.pmid","24365882"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33775"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1540-0514"],["dc.relation.issn","1073-2322"],["dc.title","REGULATION OF IRON UPTAKE IN PRIMARY CULTURE RAT HEPATOCYTES: THE ROLE OF ACUTE-PHASE CYTOKINES"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11471"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International journal of clinical and experimental pathology"],["dc.bibliographiccitation.lastpage","11479"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Moriconi, Federico"],["dc.date.accessioned","2019-07-10T08:12:06Z"],["dc.date.available","2019-07-10T08:12:06Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: The liver plays a key role in iron homeostasis during injury and hypoxia. Methods: For induction of liver injury, thioacetamide (TAA) was administered intraperitoneally to male Sprague Dawley rats. Animals were sacrificed at 0, 1, 3, 6, 12, 24, 48, 72 and 96 h. Serum, liver, spleen and heart tissues were collected from control and TAA-treated rats. Tissue sections were prepared for immunohistochemical studies. Nuclear and cytoplasmic proteins were isolated for Western blot analysis. Results: Hypoxia inducible factor (HIF)-1α and ED1 positive cells accumulated around the portal field and the interlobular space within 12 hours after TAA administration. Accordingly, Western blot analysis of liver tissue showed an early increase of HIF1α followed by a decrease at 48 h to 96 h. For Erythropoietin (EPO), as well as for HIF1- and -2α, a time-dependent translocation was observed from the cytoplasmic to the nuclear compartment. Conclusion: Our data suggest that the TAA-induced acute liver damage generates HIF-1α dependent rescue mechanisms with translocation of EPO from the cytoplasmic to the nuclear compartment. Enhanced iron transport into the liver could be necessary for increased metabolic activities during repair processes."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60864"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","1936-2625"],["dc.rights.access","openAccess"],["dc.subject","Thioacetamide (TAA); acute phase injury; hypoxia inducible factor (HIF); erythropoietin (EPO)"],["dc.subject.ddc","610"],["dc.title","Mediators of hypoxia in a rat model of sterile-induced acute liver injury"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","154"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","163"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Molina, Cristina E."],["dc.contributor.author","Tirilomis, Theodoros"],["dc.contributor.author","Kutschka, Ingo"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-26T11:03:53Z"],["dc.date.available","2019-02-26T11:03:53Z"],["dc.date.issued","2019"],["dc.description.abstract","Aims In hypertrophy and heart failure, the proarrhythmic persistent Na+ current (INaL) is enhanced. We aimed to investigate the electrophysiological role of neuronal sodium channel NaV1.8 in human hypertrophied myocardium. Methods and results Myocardial tissue of 24 patients suffering from symptomatic severe aortic stenosis and concomitant significant afterload-induced hypertrophy with preserved ejection fraction was used and compared with 12 healthy controls. We performed quantitative real-time PCR and western blot and detected a significant up-regulation of NaV1.8 mRNA (2.34fold) and protein expression (1.96-fold) in human hypertrophied myocardium compared with healthy hearts. Interestingly, NaV1.5 protein expression was significantly reduced in parallel (0.60-fold). Using whole-cell patch-clamp technique, we found that the prominent INaL was significantly reduced after addition of novel NaV1.8-specific blockers either A-803467 (30 nM) or PF-01247324 (1 μM) in human hypertrophic cardiomyocytes. This clearly demonstrates the relevant contribution of NaV1.8 to this proarrhythmic current. We observed a significant action potential duration shortening and performed confocal microscopy, demonstrating a 50% decrease in proarrhythmic diastolic sarcoplasmic reticulum (SR)-Ca2+ leak and SR-Ca2+ spark frequency after exposure to both NaV1.8 inhibitors."],["dc.identifier.doi","10.1002/ehf2.12378"],["dc.identifier.pmid","30378291"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57615"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/242"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY-NC 4.0"],["dc.title","The functional consequences of sodium channel NaV1.8 in human left ventricular hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","842"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Laboratory Investigation"],["dc.bibliographiccitation.lastpage","856"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Sheikh, Nadeem"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Schultze, Frank"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T09:09:49Z"],["dc.date.available","2018-11-07T09:09:49Z"],["dc.date.issued","2012"],["dc.description.abstract","Liver is the central organ of iron metabolism. During acute-phase-response (APR), serum iron concentration rapidly decreases. The current study aimed to compare expression and localization of iron transport protein ferroportin-1 (Fpn-1) and of other iron import proteins after experimental tissue damage induced by injecting turpentine oil in the hind limbs of rats and mice. Serum and spleen iron concentration decreased with an increase in total liver, cytoplasmic and nuclear iron concentration. In liver, mRNA amount of Fpn-1, Fpn-1a, Fpn-1b, HFE, hemojuvelin (HJV) and hephaestin (heph) genes showed a rapid decrease. Hepcidin, divalent metal transporter-1 (DMT-1), transferrin (Tf) and Tf-receptor-1 (TfR1), TfR-2 (TfR2) gene expression was increased. Western blot analysis of liver tissue lysate confirmed the changes observed at mRNA level. In spleen, a rapid decrease in gene expression of Fpn-1, Fpn-1a, Fpn-1b, DMT-1, Tf, TfR1 and TfR2, and an increase in hepcidin was observed. Immunohistochemistry of DMT-1 and TfR2 were mainly detected in the nucleus of rat liver and spleen, whereas TfR1 was clearly localized in the plasma membrane. Fpn-1 was mostly found in the nuclei of liver cells, whereas in spleen, the protein was mainly detected in the cell membrane. Western blot analysis of liver fractions confirmed immunohistochemical results. In livers of wild-type mice, gene expression of Fpn-1, Fpn-1a and Fpn-1b was downregulated, whereas hepcidin gene expression was increased. In contrast, these changes were less pronounced in IL-6ko-mice. Cytokine (IL-6, IL-1 beta and TNF-alpha) treatment of rat hepatocytes showed a downregulation of Fpn-1, Fpn-1a and Fpn-1b, and upregulation of hepcidin gene expression. Moreover, western blot analysis of cell lysate of IL-6-treated hepatocytes detected, as expected, an increase of alpha 2-macroglobulin (positive acute-phase protein), whereas albumin (negative acute-phase protein) and Fpn-1 were downregulated. Our results demonstrate that liver behaves as a 'sponge' for iron under acute-phase conditions, and Fpn-1 behaves as a negative acute-phase protein in rat hepatocytes mainly, but not exclusively, because of the effect of IL-6. These changes could explain iron retention in the cytoplasm and in the nucleus of hepatocytes during APR. Laboratory Investigation (2012) 92, 842-856; doi:10.1038/labinvest.2012.52; published online 2 April 2012"],["dc.description.sponsorship","Deutsche Krebshilfe [108774]"],["dc.identifier.doi","10.1038/labinvest.2012.52"],["dc.identifier.isi","000304730600004"],["dc.identifier.pmid","22469696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26353"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0023-6837"],["dc.title","Ferroportin-1 is a 'nuclear'-negative acute-phase protein in rat liver: a comparison with other iron-transport proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]