title: Caffeine prevents kidney stone formation by translocation of apical surface annexin A1 crystal-binding protein into cytoplasm: In vitro evidence.
abstract: Recent large 3 cohorts have shown that caffeinated beverage consumption was associated with lower risk of kidney stone disease. However, its protective mechanisms remained unknown and had not been previously investigated. We thus evaluated protective effects of caffeine (1 μM-10 mM) on calcium oxalate monohydrate (COM) kidney stone formation, using crystallization, crystal growth, cell-crystal adhesion, Western blotting, and immunofluorescence assays. The results showed that caffeine reduced crystal number but, on the other hand, increased crystal size, resulting in unchanged crystal mass, consistent with crystal growth that was not affected by caffeine. However, caffeine significantly decreased crystal-binding capacity of MDCK renal tubular cells in a dose-dependent manner. Western blotting and immunofluorescence study of COM crystal-binding proteins revealed significantly decreased level of annexin A1 on apical surface and its translocation into cytoplasm of the caffeine-treated cells, but no significant changes in other COM crystal-binding proteins (annexin A2, α-enolase, HSP70, and HSP90) were observed. Moreover, caffeine decreased intracellular [Ca2+] but increased [Ca2+] secretory index. Taken together, our findings showed an in vitro evidence of the protective mechanism of caffeine against kidney stone formation via translocation of annexin A1 from apical surface into cytoplasm to reduce the crystal-binding capacity of renal tubular epithelial cells.
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand.
authors.forename: Paleerath
authors.initials: P
authors.lastname: Peerapen
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand.
authors.forename: Visith
authors.initials: V
authors.lastname: Thongboonkerd
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002129:Calcium Oxalate / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003460:Crystallization; D003593:Cytoplasm / Q000378:metabolism*; D004285:Dogs; D042541:Intracellular Space / Q000378:metabolism; D007669:Kidney Calculi / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D061985:Madin Darby Canine Kidney Cells; D021381:Protein Transport / Q000187:drug effects
chemical_list: D017305:Annexin A1; D002129:Calcium Oxalate; D002110:Caffeine; D002118:Calcium