Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.
Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4579077?pdf=render |
| _version_ | 1819259721400451072 |
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| author | Helen P McWilliams-Koeppen James S Foster Nicole Hackenbrack Marina Ramirez-Alvarado Dallas Donohoe Angela Williams Sallie Macy Craig Wooliver Dale Wortham Jennifer Morrell-Falvey Carmen M Foster Stephen J Kennel Jonathan S Wall |
| author_facet | Helen P McWilliams-Koeppen James S Foster Nicole Hackenbrack Marina Ramirez-Alvarado Dallas Donohoe Angela Williams Sallie Macy Craig Wooliver Dale Wortham Jennifer Morrell-Falvey Carmen M Foster Stephen J Kennel Jonathan S Wall |
| author_sort | Helen P McWilliams-Koeppen |
| collection | DOAJ |
| description | Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(P)H-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils. |
| first_indexed | 2024-12-23T19:14:31Z |
| format | Article |
| id | doaj.art-7182f06f22c546f9ac3476127cafd2be |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T19:14:31Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7182f06f22c546f9ac3476127cafd2be2022-12-21T17:34:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013771610.1371/journal.pone.0137716Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.Helen P McWilliams-KoeppenJames S FosterNicole HackenbrackMarina Ramirez-AlvaradoDallas DonohoeAngela WilliamsSallie MacyCraig WooliverDale WorthamJennifer Morrell-FalveyCarmen M FosterStephen J KennelJonathan S WallLight chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(P)H-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.http://europepmc.org/articles/PMC4579077?pdf=render |
| spellingShingle | Helen P McWilliams-Koeppen James S Foster Nicole Hackenbrack Marina Ramirez-Alvarado Dallas Donohoe Angela Williams Sallie Macy Craig Wooliver Dale Wortham Jennifer Morrell-Falvey Carmen M Foster Stephen J Kennel Jonathan S Wall Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. PLoS ONE |
| title | Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. |
| title_full | Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. |
| title_fullStr | Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. |
| title_full_unstemmed | Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. |
| title_short | Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. |
| title_sort | light chain amyloid fibrils cause metabolic dysfunction in human cardiomyocytes |
| url | http://europepmc.org/articles/PMC4579077?pdf=render |
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