Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.

ABSTRACT: 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 o

SUBMITTER: McWilliams-Koeppen HP 

PROVIDER: S-EPMC4579077 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature