PMID- 17360948
OWN - NLM
STAT- MEDLINE
DCOM- 20070531
LR  - 20181201
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 18
IP  - 4
DP  - 2007 Apr
TI  - Immunoglobulin light chains generate hydrogen peroxide.
PG  - 1239-45
AB  - As low molecular weight proteins, restriction from glomerular filtration is 
      minimized, permitting significant amounts of Ig light chains to be endocytosed 
      into the proximal tubule epithelium, particularly in plasma cell dyscrasias. 
      Recent studies have shown that this effect of concentrating light chains within 
      the proximal tubule alters cell function. This study demonstrated that light 
      chains belonged to a class of proteins that are capable of catalyzing the 
      formation of hydrogen peroxide. Sufficient amounts of hydrogen peroxide were 
      produced in HK-2 cells to stimulate the production of monocyte chemoattractant 
      protein-1 (MCP-1), a key chemokine involved in monocyte/macrophage migration and 
      activation of the proximal tubule, and to increase lactate dehydrogenase release 
      into the medium. The light chain-mediated effect on MCP-1 production was 
      inhibited by co-incubation with 1,3-dimethyl-2-thiourea, which also inhibited 
      lactate dehydrogenase release, and by pyrrolidine dithiocarbamate, an inhibitor 
      of NF-kappaB. The amount of light chain that stimulated an intracellular 
      redox-signaling pathway in the proximal tubule cells was well within levels that 
      are seen in patients who have plasma cell dyscrasias. The conclusion is that 
      light chains possess a unique property that permits the development of 
      intracellular oxidative stress that in turn promotes activation of the proximal 
      tubule and elaboration of MCP-1.
FAU - Wang, Pei-Xuan
AU  - Wang PX
AD  - Division of Nephrology/Department of Medicine, 642 Lyons-Harrison Research 
      Building, 1530 Third Avenue, S., University of Alabama at Birmingham, Birmingham, 
      AL 35294-0007, USA.
FAU - Sanders, Paul W
AU  - Sanders PW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070314
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 8P30PMD17W (1,3-dimethylthiourea)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - GYV9AM2QAG (Thiourea)
SB  - IM
MH  - Catalysis
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis
MH  - Humans
MH  - Hydrogen Peroxide/*metabolism
MH  - Immunoglobulin Light Chains/*pharmacology
MH  - Kidney/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - *Oxidative Stress
MH  - Thiourea/analogs & derivatives/pharmacology
EDAT- 2007/03/16 09:00
MHDA- 2007/06/01 09:00
CRDT- 2007/03/16 09:00
PHST- 2007/03/16 09:00 [pubmed]
PHST- 2007/06/01 09:00 [medline]
PHST- 2007/03/16 09:00 [entrez]
AID - ASN.2006111299 [pii]
AID - 10.1681/ASN.2006111299 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2007 Apr;18(4):1239-45. doi: 10.1681/ASN.2006111299. Epub 2007 
      Mar 14.