Mohamed, Belal A.

[["dc.bibliographiccitation.firstpage","4655"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Endocrinology"],["dc.bibliographiccitation.lastpage","4665"],["dc.bibliographiccitation.volume","153"],["dc.contributor.author","Burnicka-Turek, Ozanna"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Shirneshan, Katayoon"],["dc.contributor.author","Thanasupawat, Thatchawan"],["dc.contributor.author","Hombach-Klonisch, Sabine"],["dc.contributor.author","Klonisch, Thomas"],["dc.contributor.author","Adham, Ibrahim M."],["dc.date.accessioned","2018-11-07T09:05:20Z"],["dc.date.available","2018-11-07T09:05:20Z"],["dc.date.issued","2012"],["dc.description.abstract","Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and beta-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and beta-cell homeostasis. (Endocrinology 153: 4655-4665, 2012)"],["dc.identifier.doi","10.1210/en.2012-1161"],["dc.identifier.isi","000309210200008"],["dc.identifier.pmid","22822165"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25294"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Endocrine Soc"],["dc.relation.issn","0013-7227"],["dc.title","INSL5-Deficient Mice Display an Alteration in Glucose Homeostasis and an Impaired Fertility"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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.firstpage","133"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","REPRODUCTION"],["dc.bibliographiccitation.lastpage","144"],["dc.bibliographiccitation.volume","142"],["dc.contributor.author","Held, Torsten"],["dc.contributor.author","Barakat, Amal Z."],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Paprotta, Ilona"],["dc.contributor.author","Meinhardt, Andreas"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Adham, Ibrahim M."],["dc.date.accessioned","2018-11-07T08:54:40Z"],["dc.date.available","2018-11-07T08:54:40Z"],["dc.date.issued","2011"],["dc.description.abstract","Heat-shock protein 110 (HSP110) family members act as nucleotide exchange factors (NEF) of mammalian and yeast HSP70 chaperones during the ATP hydrolysis cycle. In this study, we describe the expression pattern of murine HSPA4, a member of the HSP110 family, during testis development and the consequence of HSPA4 deficiency on male fertility. HSPA4 is ubiquitously expressed in all the examined tissues. During prenatal and postnatal development of gonad, HSPA4 is expressed in both somatic and germ cells; however, expression was much higher in germ cells of prenatal gonads. Analyses of Hspa4-deficient mice revealed that all homozygous mice on the hybrid C57BL/6Jx129/Sv genetic background were apparently healthy. Although HSPA4 is expressed as early as E13.5 in male gonad, a lack of histological differences between Hspa4(-/-) and control littermates suggests that Hspa4 deficiency does not impair the gonocytes or their development to spermatogonia. Remarkably, an increased number of the Hspa4-deficient males displayed impaired fertility, whereas females were fertile. The total number of spermatozoa and their motility were drastically reduced in infertile Hspa4-deficient mice compared with wild-type littermates. The majority of pachytene spermatocytes in the juvenile Hspa4(-/-) mice failed to complete the first meiotic prophase and became apoptotic. Furthermore, down-regulation of transcription levels of genes known to be expressed in spermatocytes at late stages of prophase I and post-meiotic spermatids leads to suggest that the development of most spermatogenic cells is arrested at late stages of meiotic prophase I. These results provide evidence that HSPA4 is required for normal spermatogenesis. Reproduction (2011) 142 133-144"],["dc.description.sponsorship","DAAD [A/07/80490]"],["dc.identifier.doi","10.1530/REP-11-0023"],["dc.identifier.isi","000292731400012"],["dc.identifier.pmid","21487003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22722"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bioscientifica Ltd"],["dc.relation.issn","1470-1626"],["dc.title","Heat-shock protein HSPA4 is required for progression of spermatogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","459"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","468"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Barakat, Amal Z."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Bittner, Reginald E."],["dc.contributor.author","Muehlfeld, Christian"],["dc.contributor.author","Huenlich, Mark"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Adham, Ibrahim M."],["dc.date.accessioned","2017-09-07T11:48:24Z"],["dc.date.available","2017-09-07T11:48:24Z"],["dc.date.issued","2012"],["dc.description.abstract","Failure of molecular chaperones to direct the correct folding of newly synthesized proteins leads to the accumulation of misfolded proteins in cells. HSPA4 is a member of the heat shock protein 110 family (HSP110) that acts as a nucleotide exchange factor of HSP70 chaperones. We found that the expression of HSPA4 is upregulated in murine hearts subjected to pressure overload and in failing human hearts. To investigate the cardiac function of HSPA4, Hspa4 knockout (KO) mice were generated and exhibited cardiac hypertrophy and fibrosis. Hspa4 KO hearts were characterized by a significant increase in heart weight/body weight ratio, elevated expression of hypertrophic and fibrotic gene markers, and concentric hypertrophy with preserved contractile function. In response to pressure overload, cardiac hypertrophy and remodeling were further aggravated in the Hspa4 KO compared to wild type (WT) mice. Cardiac hypertrophy in Hspa4 KO hearts was associated with enhanced activation of gp130-STAT3, CaMKII, and calcineurin-NFAT signaling. Protein blot and immunofluorescent analyses showed a significant accumulation of polyubiquitinated proteins in cardiac cells of Hspa4 KO mice. These results suggest that the myocardial remodeling of Hspa4 KO mice is due to accumulation of misfolded proteins resulting from impaired chaperone activity. Further analyses revealed a significant increase in cross sectional area of cardiomyocytes, and in expression levels of hypertrophic markers in cultured neonatal Hspa4 KO cardiomyocytes suggesting that the hypertrophy of mutant mice was a result of primary defects in cardiomyocytes. Gene expression profile in hearts of 3.5-week-old mice revealed a differentially expressed gene sets related to ion channels, muscle-specific contractile proteins and stress response. Taken together, our in vivo data demonstrate that Hspa4 gene ablation results in cardiac hypertrophy and fibrosis, possibly, through its role in protein quality control mechanism. (c) 2012 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2012.07.014"],["dc.identifier.gro","3142461"],["dc.identifier.isi","000308679700001"],["dc.identifier.pmid","22884543"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8540"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","Targeted disruption of Hspa4 gene leads to cardiac hypertrophy and fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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"]]