TY  - JOUR
  - Lordan, Sinead and O'Brien, Nora M. and Mackrill, John J.
  - 2009
  - Journal of Biochemical and Molecular Toxicology
  - The Role of Calcium in Apoptosis Induced by 7 beta-Hydroxycholesterol and Cholesterol-5 beta,6 beta-Epoxide
  - Validated
  - ()
  - 23
  - 5
  - 324
  - 332
  - Oxysterols, such as 7 beta-hydroxycholesterol (7 beta-OH) and cholesterol-5 beta,6 beta-epoxide (beta-epoxide), may have a central role in promoting atherogenesis. This is thought to be predominantly due to their ability to induce apoptosis in cells of the vascular wall and in monocytes/macrophages. Although there has been extensive research regarding the mechanisms through which oxysterols induce apoptosis, much remains to be clarified. Given that experimental evidence has long associated alterations of calcium (Ca(2+)) homeostasis to apoptotic cell death, the aim of the present study was to determine the influence of intracellular Ca(2+) changes on apoptosis induced by 7 beta-OH and P-epoxide. Ca(2+) responses in differentiated U937 cells were assessed by epifluorescence video microscopy, using the. ratiometric dye fura-2. Over 15-min exposure of differentiated U937 cells to 30 mu M of 7 beta-OH induced a slow but significant rise in fura-2 ratio. The Ca(2+) channel blocker nifedipine and the chelating agent EGTA blocked the increase in cytoplasmic Ca(2+). Moreover, dihydropyridine (DHP) binding sites identified with BODIPY-FLX-DHP were blocked following pretreatment with nifedipine, indicating that the influx of Ca(2+) occurred through L-type channels. However, following long-term incubation with 7 beta-OH, elevated levels of cytoplasmic Ca(2+) were not maintained and nifedipine did not provide protection against apoptotic cell death. Our results indicate that the increase in Ca(2+) may be an initial trigger of 7 beta-OH-induced apoptosis, but following chronic exposure to the oxysterol, the influence of Ca(2+) on apoptotic cell death appears to be less significant. In contrast, Ca(2+) did not appear to be involved in beta-epoxide-induced apoptosis. (C) 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:324-332, 2009; Published onhne in Wiley InterScience (www.interscience.wiley.com). DOI 10:1002/jbt.20295
DA  - 2009/NaN
ER  - 

@article{V113214861,
   = {Lordan, Sinead and O'Brien, Nora M. and Mackrill, John J.},
   = {2009},
   = {Journal of Biochemical and Molecular Toxicology},
   = {The Role of Calcium in Apoptosis Induced by 7 beta-Hydroxycholesterol and Cholesterol-5 beta,6 beta-Epoxide},
   = {Validated},
   = {()},
   = {23},
   = {5},
  pages = {324--332},
   = {{Oxysterols, such as 7 beta-hydroxycholesterol (7 beta-OH) and cholesterol-5 beta,6 beta-epoxide (beta-epoxide), may have a central role in promoting atherogenesis. This is thought to be predominantly due to their ability to induce apoptosis in cells of the vascular wall and in monocytes/macrophages. Although there has been extensive research regarding the mechanisms through which oxysterols induce apoptosis, much remains to be clarified. Given that experimental evidence has long associated alterations of calcium (Ca(2+)) homeostasis to apoptotic cell death, the aim of the present study was to determine the influence of intracellular Ca(2+) changes on apoptosis induced by 7 beta-OH and P-epoxide. Ca(2+) responses in differentiated U937 cells were assessed by epifluorescence video microscopy, using the. ratiometric dye fura-2. Over 15-min exposure of differentiated U937 cells to 30 mu M of 7 beta-OH induced a slow but significant rise in fura-2 ratio. The Ca(2+) channel blocker nifedipine and the chelating agent EGTA blocked the increase in cytoplasmic Ca(2+). Moreover, dihydropyridine (DHP) binding sites identified with BODIPY-FLX-DHP were blocked following pretreatment with nifedipine, indicating that the influx of Ca(2+) occurred through L-type channels. However, following long-term incubation with 7 beta-OH, elevated levels of cytoplasmic Ca(2+) were not maintained and nifedipine did not provide protection against apoptotic cell death. Our results indicate that the increase in Ca(2+) may be an initial trigger of 7 beta-OH-induced apoptosis, but following chronic exposure to the oxysterol, the influence of Ca(2+) on apoptotic cell death appears to be less significant. In contrast, Ca(2+) did not appear to be involved in beta-epoxide-induced apoptosis. (C) 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:324-332, 2009; Published onhne in Wiley InterScience (www.interscience.wiley.com). DOI 10:1002/jbt.20295}},
  source = {IRIS}
}