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J Investig Med. 1999 Nov;47(9):496-501.

Inhibition of Na-K-ATPase activity and gene expression by a myeloma light chain in proximal tubule cells.

Author information

1
Department of Medicine, Nephrology Section, Tulane University School of Medicine, New Orleans, LA 70112, USA.

Abstract

BACKGROUND:

Light chain nephrotoxicity is frequently associated with Fanconi syndrome characterized by amino-aciduria, glycosuria, phosphaturia, and bicarbonaturia. The mechanisms of these transport abnormalities are unknown. To determine the role of Na-K-ATPase, we examined the effects of a lambda-light chain on both the activity and gene expression of Na-K-ATPase in primary cultures of rat proximal tubule cells.

METHODS:

The lambda-light chain used here was isolated from urine of a patient with multiple myeloma and previously shown to inhibit sodium-dependent phosphate and glucose transport in proximal tubule cells. Na-K-ATPase was determined spectrophotometrically and the gene expression by Northern analysis in cells exposed to light chain.

RESULTS:

In cells exposed to 200 mumol/L light chain Na-K-ATPase activity was reduced significantly, up to 73%, at 2, 24, and 48 hours compared with control cells (N = 12, P < 0.001). Northern analysis showed that in cells exposed to light chain for 24 and 48 hours the message for the alpha-1 isoform of Na-K-ATPase was suppressed significantly compared with control cells. The messages for GAPDH, beta-actin, and 28 S RNA in light chain exposed cells were also depressed in comparison with control cells. This light chain also significantly inhibited thymidine incorporation by proximal tubule cells in a dose-dependent manner.

CONCLUSIONS:

These data suggest a general toxicity to cells by this light chain and indicate that inhibitory effects on both the activity and gene expression of Na-K-ATPase may be an important mechanism of light chain cytotoxicity on proximal tubule cells.

PMID:
10572380
[Indexed for MEDLINE]

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