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Updated: Aug 15, 2026

Cytosolic Calcium Measurements in Renal Epithelial Cells by Flow Cytometry
Published on: October 28, 2014
Immunoglobulin light chain alters mesangial cell calcium homeostasis
L Zhu1, G A Herrera, C R White
1Department of Pathology, University of Alabama at Birmingham, 35294-0007, USA.
Insights
Certain immunoglobulin light chains disrupt mesangial cell calcium signaling, potentially causing glomerulosclerosis. Myo-inositol supplementation partially reversed these effects, suggesting a therapeutic target for kidney disease.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Immunoglobulin light chains are implicated in kidney disease pathogenesis.
- Mesangial cell calcium homeostasis is crucial for kidney function.
- Dysregulation of intracellular calcium can lead to cellular dysfunction and disease.
Purpose of the Study:
- To investigate if specific immunoglobulin light chains directly alter mesangial cell calcium homeostasis.
- To elucidate the role of kappa-light chains in regulating intracellular calcium signaling in rat mesangial cells.
- To explore the potential therapeutic effect of myo-inositol on light chain-induced calcium dysregulation.
Main Methods:
- Measurement of intracellular calcium concentration ([Ca2+]) in rat mesangial cells using fura 2.
- Assessment of ATP-, thrombin-, and thapsigargin-evoked calcium transients and influx.
- Treatment of mesangial cells with a glomerulopathic kappa-light chain (gle) and myo-inositol.
Main Results:
- Glomerulopathic kappa-light chain (gle) significantly attenuated ATP- and thrombin-evoked calcium transients and influx.
- Myo-inositol supplementation partially reversed the gle-induced attenuation of ATP-evoked calcium signaling.
- Gle also decreased thapsigargin-induced calcium transients and influx, an effect not reversed by myo-inositol.
- A different kappa-light chain did not impact mesangial cell calcium signaling.
Conclusions:
- Specific immunoglobulin light chains, like gle, can derange mesangial cell calcium homeostasis.
- This disruption of calcium signaling may contribute to the pathogenesis of glomerulosclerosis.
- Myo-inositol shows potential in mitigating some light chain-induced calcium dysregulation, warranting further investigation.
Abstract:
This study examined the hypothesis that certain immunoglobulin light chains directly altered mesangial cell calcium homeostasis. Intracellular Ca2+ concentration (intracellular [Ca2+]) signaling was determined in suspensions of rat mesangial cells using the acetoxymethyl ester of fura 2 with a calcium removal/replacement protocol. Pretreatment of cultured rat mesangial cells with a glomerulopathic kappa-light chain (gle) produced reversible dose- and time-dependent attenuation of ATP- and thrombin-evoked [Ca2+] transients (189 +/- 24 vs. 126 +/- 10 nM, P < 0.05 with ATP; 198 +/- 5 vs. 117 +/- 3 nM, P < 0.05 with thrombin) and capacitative calcium influx (199 +/- 14 vs. 142 +/- 17 nM, P < 0.05 for ATP; 252 +/- 19 vs. 198 +/- 18 nM, P < 0.05 for thrombin). Mesangial cells treated with gle and supplemented with myo-inositol (450 microM) did not demonstrate the attenuation of the ATP-evoked [Ca2+] transient and capacitative calcium influx. Gle also decreased mean [Ca2+] transient (80 +/- 7 vs. 56 +/- 1 nM, P < 0.05) and capacitative calcium influx (306 +/- 10 vs. 241 +/- 4 nM, P < 0.05) in response to thapsigargin, a Ca2+-adenosinetriphosphatase inhibitor. This inhibition was not reversed by exogenous myo-inositol. Another kappa-light chain (10 microg/ml) did not affect mesangial cell calcium signaling. Deranged mesangial cell calcium homeostasis by certain light chains may play a central pathogenetic role in glomerulosclerosis associated with deposition of immunoglobulin light chains.
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