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Glucosylceramide sy...
Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
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- Andersson, Linda, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Cinato, Mathieu (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Mardani, Ismena (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Miljanovic, Azra, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Arif, Muhammad (author)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Koh, Ara (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Lindbom, Malin, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Laudette, Marion, 1992 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Bollano, Entela, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Omerovic, Elmir, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Klevstig, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Henricsson, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Fogelstrand, Per, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Swärd, Karl (author)
- Department of Experimental Medical Science, Lund University, Lund, Sweden,Lund Univ, Dept Expt Med Sci, SE-22184 Lund, Sweden.
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- Ekstrand, Matias (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Levin, Max, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Wikström, Johannes, 1977 (author)
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Mölndal, Sweden,AstraZeneca Gothenburg, BioPharmaceut R&D, Biosci Res & Early Dev Cardiovasc Renal & Metab, Pepparedsleden 1, SE-43183 Mölndal, Sweden.
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- Doran, Stephen (author)
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK,Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
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- Hyötyläinen, Tuulia, 1971- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik,Örebro Univ, Sch Nat Sci & Technol, Fakultetsgatan 1, SE-70182 Örebro, Sweden.
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- Sinisalu, Lisanna, 1993- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik,Örebro Univ, Sch Nat Sci & Technol, Fakultetsgatan 1, SE-70182 Örebro, Sweden.
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- Oresic, Matej, 1967- (author)
- Karolinska Institutet,Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku, Turku, Finland,Örebro Univ, Sch Med Sci, SE-70182 Örebro, Sweden.;Univ Turku, Turku Biosci Ctr, FIN-20521 Turku, Finland.
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- Tivesten, Åsa, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Adiels, Martin, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Bergo, Martin O. (author)
- Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden,Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.
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- Proia, Richard (author)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA,NIDDK, NIH, Bethesda, MD 20892 USA.
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- Mardinoglu, Adil (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
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- Jeppsson, Anders, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Levin, Malin, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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(creator_code:org_t)
- 2021-06-23
- 2021
- English.
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
- Related links:
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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https://gup.ub.gu.se...
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Abstract
Subject headings
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- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Cardiac dysfunction
- Endolysosomal trafficking
- Adrenergic
- Autophagy
- Beta
- Glycosphingolipids
- Lipids
- Receptors
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Andersson, Linda ...
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Cinato, Mathieu
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Mardani, Ismena
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Miljanovic, Azra ...
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Arif, Muhammad
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Koh, Ara
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show more...
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Lindbom, Malin, ...
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Laudette, Marion ...
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Bollano, Entela, ...
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Omerovic, Elmir, ...
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Klevstig, Martin ...
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Henricsson, Marc ...
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Fogelstrand, Per ...
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Swärd, Karl
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Ekstrand, Matias
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Levin, Max, 1969
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Wikström, Johann ...
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Doran, Stephen
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Hyötyläinen, Tuu ...
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Sinisalu, Lisann ...
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Oresic, Matej, 1 ...
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Tivesten, Åsa, 1 ...
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Adiels, Martin, ...
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Bergo, Martin O.
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Proia, Richard
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Mardinoglu, Adil
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Jeppsson, Anders ...
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Borén, Jan, 1963
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Levin, Malin, 19 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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European Heart J ...
- By the university
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Örebro University
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Royal Institute of Technology
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Karolinska Institutet
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University of Gothenburg