Inhibition of Na,K-ATPase causes opacification of the lens through abnormal increases in sodium and calcium levels, disturbed osmotic equilibrium, activation of proteolytic enzymes and cell damage. We previously identified Translationally Controlled Tumor Protein (TCTP) as a cytoplasmic repressor of Na,K-ATPase and confirmed that systemic hypertension is induced in transgenic mice over-expressing TCTP through inhibition of vascular Na,K-ATPase and increased intracellular calcium mobilization. In the current study, we confirmed the role of TCTP in causing intracellular calcium mobilization by inhibiting Na,K-ATPase in a human lens epithelial cell line and further showed that some of the TCTP-transgenic mice develop cataracts with an incidence rate of 7.38% compared to 1.47% in controls. We demonstrated that TCTP acts as a cataractogenic factor through the repression of Na, K-ATPase activity and calcium mobilization in lens epithelial cells.
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Acknowledgments This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2007-000-20263-0); Seoul R&BD Program (10541); and the NCRC program of MOST/KOSEF (R15-2006-020) through the Center for Cell Signalling & Drug Discovery at Ewha Womans University.
- Intracellular calcium
- Translationally Controlled Tumor Protein (TCTP)