Over-expression of translationally controlled tumor protein in lens epithelial cells seems to be associated with cataract development.
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.
Kim
Min-Jeong
MJ
College of Pharmacy, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Lyu
Jungmook
J
Sohn
Kyu-Been
KB
Kim
Miyoung
M
Cho
Myeong-Chan
MC
Joo
Choun-Ki
CK
Lee
Kyunglim
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002386:Cataract / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D014176:Protein Biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium