Involvement of Fas Signalling In 7 Beta-Hydroxycholesterol- and Cholesterol-5 Beta,6 Beta-Epoxide-Induced Apoptosis

Typeset version

 

TY  - JOUR
  - Lordan, S, Mackrill, JJ, O'Brien, NM
  - 2008
  - August
  - International Journal of Toxicology
  - Involvement of Fas Signalling In 7 Beta-Hydroxycholesterol- and Cholesterol-5 Beta,6 Beta-Epoxide-Induced Apoptosis
  - Validated
  - ()
  - 27
  - 3
  - 279
  - 285
  - The induction of apoptosis in cells of the arterial wall is a critical event in the development of atheroma. 7 beta-Hydroxycholesterol (7 beta-OH) and cholesterol-5 beta, 6 beta-epoxide (beta-epoxide) are components of oxLDL and have previously been shown to be potent inducers of apoptosis. However, the exact mechanisms through which these oxysterols induce apoptosis remains to be fully elucidated. The specific interaction of the Fas death receptor with Fas ligand (FasL) initiates a caspase cascade culminating in apoptosis. The purpose of the present study was to determine the involvement of Fas signalling in 7 beta-OH-and beta-epoxide-induced apoptosis. To this end we employed the Fas/FasL antagonist, Kp7-6, and examined the effect of Fas inhibition on oxysterol-induced cell death in U937 cells. Fas levels were increased following 24 h exposure to 30 mu M 7 beta-OH while treatment with 30 mu M beta-epoxide had no effect. Kp7-6 reduced the Fas content of 7 beta-OH-treated cells to control levels and partially protected against 7 beta-OH-induced apoptosis. This coincided with a decrease in cytochrome c release along with a reduction in caspase-3 and caspase-8 activity. Our data implicate Fas signalling in the apoptotic pathway induced by 7 beta-OH and also highlight differences between apoptosis induced by 7 beta-OH and beta-epoxide..
  - DOI 10.1080/10915810802208616
DA  - 2008/08
ER  - 
@article{V723577,
   = {Lordan,  S and  Mackrill,  JJ and  O'Brien,  NM },
   = {2008},
   = {August},
   = {International Journal of Toxicology},
   = {Involvement of Fas Signalling In 7 Beta-Hydroxycholesterol- and Cholesterol-5 Beta,6 Beta-Epoxide-Induced Apoptosis},
   = {Validated},
   = {()},
   = {27},
   = {3},
  pages = {279--285},
   = {{The induction of apoptosis in cells of the arterial wall is a critical event in the development of atheroma. 7 beta-Hydroxycholesterol (7 beta-OH) and cholesterol-5 beta, 6 beta-epoxide (beta-epoxide) are components of oxLDL and have previously been shown to be potent inducers of apoptosis. However, the exact mechanisms through which these oxysterols induce apoptosis remains to be fully elucidated. The specific interaction of the Fas death receptor with Fas ligand (FasL) initiates a caspase cascade culminating in apoptosis. The purpose of the present study was to determine the involvement of Fas signalling in 7 beta-OH-and beta-epoxide-induced apoptosis. To this end we employed the Fas/FasL antagonist, Kp7-6, and examined the effect of Fas inhibition on oxysterol-induced cell death in U937 cells. Fas levels were increased following 24 h exposure to 30 mu M 7 beta-OH while treatment with 30 mu M beta-epoxide had no effect. Kp7-6 reduced the Fas content of 7 beta-OH-treated cells to control levels and partially protected against 7 beta-OH-induced apoptosis. This coincided with a decrease in cytochrome c release along with a reduction in caspase-3 and caspase-8 activity. Our data implicate Fas signalling in the apoptotic pathway induced by 7 beta-OH and also highlight differences between apoptosis induced by 7 beta-OH and beta-epoxide..}},
   = {DOI 10.1080/10915810802208616},
  source = {IRIS}
}
AUTHORSLordan, S, Mackrill, JJ, O'Brien, NM
YEAR2008
MONTHAugust
JOURNAL_CODEInternational Journal of Toxicology
TITLEInvolvement of Fas Signalling In 7 Beta-Hydroxycholesterol- and Cholesterol-5 Beta,6 Beta-Epoxide-Induced Apoptosis
STATUSValidated
TIMES_CITED()
SEARCH_KEYWORD
VOLUME27
ISSUE3
START_PAGE279
END_PAGE285
ABSTRACTThe induction of apoptosis in cells of the arterial wall is a critical event in the development of atheroma. 7 beta-Hydroxycholesterol (7 beta-OH) and cholesterol-5 beta, 6 beta-epoxide (beta-epoxide) are components of oxLDL and have previously been shown to be potent inducers of apoptosis. However, the exact mechanisms through which these oxysterols induce apoptosis remains to be fully elucidated. The specific interaction of the Fas death receptor with Fas ligand (FasL) initiates a caspase cascade culminating in apoptosis. The purpose of the present study was to determine the involvement of Fas signalling in 7 beta-OH-and beta-epoxide-induced apoptosis. To this end we employed the Fas/FasL antagonist, Kp7-6, and examined the effect of Fas inhibition on oxysterol-induced cell death in U937 cells. Fas levels were increased following 24 h exposure to 30 mu M 7 beta-OH while treatment with 30 mu M beta-epoxide had no effect. Kp7-6 reduced the Fas content of 7 beta-OH-treated cells to control levels and partially protected against 7 beta-OH-induced apoptosis. This coincided with a decrease in cytochrome c release along with a reduction in caspase-3 and caspase-8 activity. Our data implicate Fas signalling in the apoptotic pathway induced by 7 beta-OH and also highlight differences between apoptosis induced by 7 beta-OH and beta-epoxide..
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ISBN_ISSN
EDITION
URL
DOI_LINKDOI 10.1080/10915810802208616
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