Size-dependent cellular uptake mechanism and cytotoxicity toward calcium oxalate on Vero cells.
Urinary crystals with various sizes are present in healthy individuals and patients with kidney stone; however, the cellular uptake mechanism of calcium oxalate of various sizes has not been elucidated. This study aims to compare the internalization of nano-/micron-sized (50 nm, 100 nm, and 1 μm) calcium oxalate monohydrate (COM) and dihydrate (COD) crystals in African green monkey renal epithelial (Vero) cells. The internalization and adhesion of COM and COD crystals to Vero cells were enhanced with decreasing crystal size. Cell death rate was positively related to the amount of adhered and internalized crystals and exhibited higher correlation with internalization than that with adhesion. Vero cells mainly internalized nano-sized COM and COD crystals through clathrin-mediated pathways as well as micron-sized crystals through macropinocytosis. The internalized COM and COD crystals were distributed in the lysosomes and destroyed lysosomal integrity to some extent. The results of this study indicated that the size of crystal affected cellular uptake mechanism, and may provide an enlightenment for finding potential inhibitors of crystal uptake, thereby decreasing cell injury and the occurrence of kidney stones.
Department of Chemistry, Jinan University, Guangzhou 510632, China; Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632, China.
Xin-Yuan
XY
Sun
Department of Chemistry, Jinan University, Guangzhou 510632, China; Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632, China.
Qiong-Zhi
QZ
Gan
Department of Chemistry, Jinan University, Guangzhou 510632, China; Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632, China.
Jian-Ming
JM
Ouyang
D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism* / Q000633:toxicity; D002522:Chlorocebus aethiops; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004705:Endocytosis; D014709:Vero Cells
D002129:Calcium Oxalate