Mohamed, Belal A.

[["dc.bibliographiccitation.artnumber","9889"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Jakubiczka-Smorag, Joanna"],["dc.contributor.author","Buchholz, Eric"],["dc.contributor.author","Koszewa, Sabrina"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2019-08-06T11:25:13Z"],["dc.date.available","2019-08-06T11:25:13Z"],["dc.date.issued","2019"],["dc.description.abstract","Calcium/calmodulin-dependent protein kinase type II delta (CaMKIIδ), the predominant CaMKII isoform expressed in the heart, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling. However, the role of CaMKIIδ in volume overload (VO) has not been explored. We have previously reported an activation of CaMKII during transition to HF in long-term VO. Here, we address whether CaMKIIδ is critically involved in the mortality, myocardial remodeling, and heart failure (HF) progression in response to VO. CaMKIIδ knockout (δ-KO) and wild-type (WT) littermates were exposed to aortocaval shunt-induced VO, and the progression of adverse myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses. The mortality rates during 10 weeks of VO were similar in δ-KO and WT mice. Both genotypes displayed comparable eccentric myocardial hypertrophy, altered left ventricle geometry, perturbed systolic and diastolic functions after shunt. Additionally, cardiomyocytes hypertrophy, augmented myocyte apoptosis, and up-regulation of hypertrophic genes were also not significantly different in δ-KO versus WT hearts after shunt. Therefore, CaMKIIδ signaling seems to be dispensable for the progression of VO-induced maladaptive cardiac remodeling. Accordingly, we hypothesize that CaMKIIδ-inhibition as a therapeutic approach might not be helpful in the context of VO-triggered HF."],["dc.identifier.doi","10.1038/s41598-019-46332-3"],["dc.identifier.pmid","31285482"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16358"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62306"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/281"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["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","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","2045-2322"],["dc.relation.issn","2045-2322"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Genetic deletion of calcium/calmodulin-dependent protein kinase type II delta does not mitigate adverse myocardial remodeling in volume-overloaded hearts"],["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","817"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","American Journal of Respiratory Cell and Molecular Biology"],["dc.bibliographiccitation.lastpage","824"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Barakat, Amal Z."],["dc.contributor.author","Held, Torsten"],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Muehlfeld, Christian"],["dc.contributor.author","Maenner, Joerg"],["dc.contributor.author","Adham, Ibrahim M."],["dc.date.accessioned","2018-11-07T09:41:50Z"],["dc.date.available","2018-11-07T09:41:50Z"],["dc.date.issued","2014"],["dc.description.abstract","Heat shock proteins HSPA4L and HSPA4 are closely related members of the HSP110 family and act as cochaperones. We generated Hspa4l(-1-) Hspa4(-1-) mice to investigate a functional complementarity between HSPA4L and HSPA4 during embryonic development. Hspa4l(-1-) Hspa4(-1-) 2 embryos exhibited marked pulmonary hypoplasia and neonatal death. Compared with lungs of wild- type, Hspa4l(-1-) , and Hspa4(-1-) embryos, Hspa4l(-1-) Hspa4(-1-) lungs were characterized by diminished saccular spaces and increased mesenchymal septa. Mesenchymal hypercellularity was determined to be due to an increased cell proliferation index and decreased cell death. A significant increase in expression levels of prosurvival protein B cell leukemia/ lymphoma 2 may be the cause for inhibition of apoptotic process in lungs of Hspa4(-1-) Hspa4l(-1-) embryos. Accumulation of glycogen and diminished expression of surfactant protein B, prosurfactant protein C, and aquaporin 5 in saccular epithelium suggested impaired maturation of type II and type I pneumocytes in the Hspa4l(-1-) Hspa4(-1-) lungs. Further experiments showed a significant accumulation of ubiquitinated proteins in the lungs of Hspa4l(-1-) Hspa4(-1-) embryos, indicating an impaired chaperone activity. Our study demonstrates that HSPA4L and HSPA4 collaborate in embryonic lung maturation, which is necessary for adaptation to air breathing at birth."],["dc.identifier.doi","10.1165/rcmb.2013-0132OC"],["dc.identifier.isi","000334403900016"],["dc.identifier.pmid","23980576"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33820"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Thoracic Soc"],["dc.relation.issn","1535-4989"],["dc.relation.issn","1044-1549"],["dc.title","Respiratory Distress and Early Neonatal Lethality in Hspa4l/Hspa4 Double-Mutant Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","The FEBS Journal"],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Nyamsuren, Gunsmaa"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Adham, Ibrahim M."],["dc.contributor.author","Mohamed, Belal A."],["dc.date.accessioned","2021-04-14T08:23:52Z"],["dc.date.available","2021-04-14T08:23:52Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1111/febs.15643"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81077"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1742-4658"],["dc.relation.issn","1742-464X"],["dc.title","Perturbed differentiation of murine embryonic stem cells upon Pelota deletion due to dysregulated FOXO1/β‐catenin signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","229"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Translational Medicine"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Barakat, Amal Z."],["dc.contributor.author","Held, Torsten"],["dc.contributor.author","Rodrigues, Daniel M."],["dc.contributor.author","Mobarak, Sherok"],["dc.contributor.author","Swarnka, Surabhi"],["dc.contributor.author","Adham, Ibrahim M."],["dc.contributor.author","Mohamed, Belal A."],["dc.date.accessioned","2022-06-01T09:39:42Z"],["dc.date.accessioned","2022-08-12T13:52:22Z"],["dc.date.available","2022-06-01T09:39:42Z"],["dc.date.available","2022-08-12T13:52:22Z"],["dc.date.issued","2022-05-14"],["dc.date.updated","2022-07-29T12:17:34Z"],["dc.description.abstract","Background\r\n Molecular chaperones assist protein folding, facilitate degradation of misfolded polypeptides, and thereby maintain protein homeostasis. Impaired chaperone activity leads to defective protein quality control that is implicated in multiple skeletal muscle diseases. The heat shock protein A4 (HSPA4) acts as a co-chaperone for HSP70. Previously, we showed that Hspa4 deletion causes impaired protein homeostasis in the heart. However, its functional role in skeletal muscle has not been explored.\r\n \r\n \r\n Methods\r\n We performed a comparative phenotypic and biochemical analyses of Hspa4 knockout (KO) mice with wild-type (WT) littermates.\r\n \r\n \r\n Results\r\n HSPA4 is markedly upregulated in regenerating WT muscle in vivo, and in differentiated myoblasts in vitro. Hspa4-KO mice are marked by growth retardation and increased variability in body weight, accompanied by 35% mortality rates during the peri-weaning period. The surviving Hspa4-KO mice experienced progressive skeletal muscle myopathy, characterized by increased number of muscle fibers with centralized nuclei, heterogeneous myofiber size distribution, inflammatory cell infiltrates and upregulation of embryonic and perinatal myosin heavy chain transcripts. Hspa4-KO muscles demonstrated an accumulation of autophagosome-associated proteins including microtubule associated protein1 light chain 3-II (LC3-II) and p62/sequestosome accompanied by increased number of TUNEL-positive nuclei.\r\n \r\n \r\n Conclusions\r\n Our findings underscore the indispensable role of HSPA4 in maintenance of muscle integrity through contribution in skeletal muscle autophagy and apoptosis, which might provide a novel therapeutic strategy for skeletal muscle morbidities."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship"," Deutsche Stiftung für Herzforschung"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","Journal of Translational Medicine. 2022 May 14;20(1):229"],["dc.identifier.doi","10.1186/s12967-022-03418-3"],["dc.identifier.pii","3418"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112725"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","1479-5876"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","HSPs"],["dc.subject","Myopathy"],["dc.subject","Autophagy"],["dc.title","Heat shock protein A4 ablation leads to skeletal muscle myopathy associated with dysregulated autophagy and induced apoptosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4440"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Journal of Cellular and Molecular Medicine"],["dc.bibliographiccitation.lastpage","4452"],["dc.bibliographiccitation.volume","26"],["dc.contributor.affiliation","Mohamed, Belal A.; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Elkenani, Manar; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Mobarak, Sherok; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Marques Rodrigues, Daniel; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Annamalai, Karthika; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Schnelle, Moritz; 2\r\nDZHK (German Centre for Cardiovascular Research)\r\nGöttingen Germany"],["dc.contributor.affiliation","Bader, Michael; 4\r\nMax‐Delbrück‐Center for Molecular Medicine (MDC)\r\nBerlin‐Buch Germany"],["dc.contributor.affiliation","Hasenfuss, Gerd; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Mobarak, Sherok"],["dc.contributor.author","Marques Rodrigues, Daniel"],["dc.contributor.author","Annamalai, Karthika"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Bader, Michael"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2022-08-12T11:32:54Z"],["dc.date.available","2022-08-12T11:32:54Z"],["dc.date.issued","2022-08"],["dc.date.updated","2022-11-11T13:14:07Z"],["dc.description.abstract","Adrenergic stimulation in the heart activates the protein kinase A (PKA), which phosphorylates key proteins involved in intracellular Ca2+ handling. PKA is held in proximity to its substrates by protein scaffolds, the A kinase anchoring proteins (AKAPs). We have previously identified the transcript of phosphodiesterase 4D interacting protein (Pde4dip; also known as myomegalin), one of the sarcomeric AKAPs, as being differentially expressed following hemodynamic overload, a condition inducing hyperadrenergic state in the heart. Here, we addressed whether PDE4DIP is involved in the adverse cardiac remodelling following hemodynamic stress. Homozygous Pde4dip knockout (KO) mice, generated by CRISPR-Cas9 technology, and wild-type (WT) littermates were exposed to aortocaval shunt (shunt) or transthoracic aortic constriction (TAC) to induce hemodynamic volume overload (VO) or pressure overload (PO), respectively. The mortality, cardiac structure, function and pathological cardiac remodelling were followed up after hemodynamic injuries. The PDE4DIP protein level was markedly downregulated in volume-overloaded- but upregulated in pressure-overloaded-WT hearts. Following shunt or TAC, mortality rates were comparably increased in both genotypes. Twelve weeks after shunt or TAC, Pde4dip-KO animals showed a similar degree of cardiac hypertrophy, dilatation and dysfunction as WT mice. Cardiomyocyte hypertrophy, myocardial fibrosis, reactivation of cardiac stress genes and downregulation of ATPase, Ca2+ transporting, cardiac muscle, slow twitch 2 transcript did not differ between WT and Pde4dip-KO hearts following shunt or TAC. In summary, despite a differential expression of PDE4DIP protein in remodelled WT hearts, Pde4dip deficiency does not modulate adverse cardiac remodelling after hemodynamic VO or PO."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1111/jcmm.17468"],["dc.identifier.pmid","35860864"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112714"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/442"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation.eissn","1582-4934"],["dc.relation.issn","1582-1838"],["dc.relation.issn","1582-4934"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","Hemodynamic stress-induced cardiac remodelling is not modulated by ablation of phosphodiesterase 4D interacting protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]