TY - JOUR
T1 - Cytotoxicity of amyloidogenic immunoglobulin light chains in cell culture
AU - Sikkink, L. A.
AU - Ramirez-Alvarado, M.
N1 - Funding Information:
Acknowledgements. We thank Doug Martin and Yeng Her for their fibril-formation data for AL-09 and kI O18/O8 and the Ramirez-Alvarado laboratory for helpful discussions. This study was supported by NIH GM071514, the generous support of amyloidosis patients and the Mayo Foundation.
PY - 2010/11
Y1 - 2010/11
N2 - Light-chain amyloidosis (AL) is a devastating protein-misfolding disease characterized by abnormal proliferation of plasma cells in the bone marrow that secrete monoclonal immunoglobulin light chains that misfold and form amyloid fibrils, thus causing organ failure and death. Numerous reports on different protein-misfolding diseases show that soluble oligomeric species populated by amyloidogenic proteins can be quite toxic to cells. However, it is not well established whether the soluble immunoglobulin light-chain species found in circulation in patients with AL are toxic to cells in target organs. We determined the cellular toxicity of two well-characterized light-chain variable domain proteins from cardiac AL patients and their corresponding germline protein, devoid of somatic mutations. Our results show that the soluble form of the AL proteins we characterized are toxic to cardiomyocytes, and that the species found in cell culture correspond, for the most part, to the species present in circulation in these patients.
AB - Light-chain amyloidosis (AL) is a devastating protein-misfolding disease characterized by abnormal proliferation of plasma cells in the bone marrow that secrete monoclonal immunoglobulin light chains that misfold and form amyloid fibrils, thus causing organ failure and death. Numerous reports on different protein-misfolding diseases show that soluble oligomeric species populated by amyloidogenic proteins can be quite toxic to cells. However, it is not well established whether the soluble immunoglobulin light-chain species found in circulation in patients with AL are toxic to cells in target organs. We determined the cellular toxicity of two well-characterized light-chain variable domain proteins from cardiac AL patients and their corresponding germline protein, devoid of somatic mutations. Our results show that the soluble form of the AL proteins we characterized are toxic to cardiomyocytes, and that the species found in cell culture correspond, for the most part, to the species present in circulation in these patients.
KW - Apoptosis
KW - Cellular toxicity
KW - Immunoglobulin light chain
KW - Light-chain amyloidosis
KW - Protein misfolding
UR - http://www.scopus.com/inward/record.url?scp=79958709932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958709932&partnerID=8YFLogxK
U2 - 10.1038/cddis.2010.75
DO - 10.1038/cddis.2010.75
M3 - Article
C2 - 21368874
AN - SCOPUS:79958709932
SN - 2041-4889
VL - 1
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 11
M1 - e98
ER -