title: Deficiency of calcium and magnesium induces apoptosis via scavenger receptor BI.
abstract: OBJECTIVE
  Cells undergo apoptosis in stressed status such as in intracellular calcium overload or extracellular calcium/magnesium deficiency. The mechanisms of how deficiency of the divalent metal ions induces apoptosis remain to be defined. Scavenger receptor BI (SR-BI) is a high density lipoprotein (HDL) receptor. Recent studies demonstrated that SR-BI is a stress response molecule which induces apoptosis upon serum deprivation. In this study, we assessed our hypothesis that the deficiency of calcium/magnesium induces apoptosis via SR-BI apoptotic pathway.
  
  
  METHODS
  We employed CHO cell lines expressing vector and SR-BI to test the effect of SR-BI on apoptosis induced by deficiency of calcium, magnesium and zinc in culture medium. The regain of different metal ions in deficient medium was also performed, respectively. Cell death was detected by morphological changes and quantified by LDH cytotoxicity assay. Apoptosis was also assessed by DNA ladder assay and DNA condensation assay. The SR-BIC323G mutant cells which lack the apoptotic activity of SR-BI were employed to verify the SR-BI-dependent effect on calcium/magnesium induced apoptosis.
  
  
  RESULTS
  The deficiency of calcium/magnesium induced cell apoptosis in CHO-SR-BI cells, but not in CHO-vector cells. Moreover, no apoptotic cell death was observed in SR-BIC323G mutant cells, indicating that the deficiency of divalent metal ions induces apoptosis in a SR-BI-dependent manner. Furthermore, the restoration of calcium or magnesium, but not zinc, protected CHO-SR-BI cells from apoptotic cell death, in a dose-dependent fashion.
  
  
  CONCLUSIONS
  These findings extend our understanding about how calcium and magnesium deficiency induces apoptosis.
authors.affiliation: Department of Pediatrics, University of Kentucky Medical School, Lexington, KY 40536, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Feng
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.forename: Haiqing
authors.initials: H
authors.lastname: Gao
authors.forename: Xiang-An
authors.initials: XA
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D016466:CHO Cells; D002118:Calcium / Q000172:deficiency*; D018929:Cell Culture Techniques; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000235:genetics; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D008275:Magnesium Deficiency; D009154:Mutation; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000502:physiology*
chemical_list: D003470:Culture Media; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D008274:Magnesium; D002118:Calcium