Delayed apoptosis post-cadmium injury in renal proximal tubule epithelial cells

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Abstract

Background: Accumulation of the widespread environmental toxin cadmium (Cd) in the kidney results initially in proximal tubule dysfunction. Exposure to Cd has been previously shown to induce apoptosis in LLC-PK (Lily Laboratory Culture, Porcine Kidney) cells, which are a model of proximal tubule epithelium. Hypothesis: We postulated that modulation of the components of the apoptotic pathway triggered by Cd is amenable to therapeutic intervention. Methods: We subjected confluent LLC-PK cells grown on two-compartment filters and on plastic to Cd (1-50 μM). Apoptosis and changes in components of the apoptotic pathway were measured by immunocytochemical and immunoblot analysis during the period of exposure and following Cd withdrawal. Results: Insignificant apoptosis was seen during exposure to Cd and immediately after removal of this metal. Two waves of apoptosis were noted 6 and 48 h after the Cd was removed from the apical compartment. The apoptosis 48 h post-Cd exposure was accompanied by a decrease in cellular ATP levels and transepithelial resistance and preceded by an increase in p38 phosphorylation. Inhibition of p38 mitogen-activated protein kinase activity decreased the delayed apoptotic peak, without affecting the rate of recovery of the integrity of the renal epithelium. IGF-1 neither altered the delayed apoptosis nor facilitated the rate of recovery of the integrity of the renal epithelium. Conclusion: We demonstrate that following exposure to Cd, renal epithelial cells undergo significant apoptosis, which appears to involve p38 and is not amenable to IGF therapy. Copyright © 2003 S. Karger AG, Basel.

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Stinson, L. J., Darmon, A. J., Dagnino, L., & D’Souza, S. J. A. (2003). Delayed apoptosis post-cadmium injury in renal proximal tubule epithelial cells. American Journal of Nephrology, 23(1), 27–37. https://doi.org/10.1159/000066298

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