The p17 cleaved form of caspase-3 is present within viable macrophages in vitro and in atherosclerotic plaque

Arteriosclerosis, Thrombosis, and Vascular Biology
Thomas Q NhanStephen M Schwartz

Abstract

In vitro studies of macrophage death in response to oxidized LDL (oxLDL) were undertaken as a model for the formation of the necrotic core of atherosclerotic plaque. Thioglycollate-elicited mouse peritoneal macrophages avidly incorporated both oxLDL and acetylated LDL (acLDL) to become foam cells. oxLDL-treated macrophages, but not acLDL-treated macrophages, showed nearly 100% death, with characteristics consistent with apoptosis, including cell surface phosphatidylserine exposure, intracellular caspase-3 activity, cleavage of caspase-3 substrates, and DNA fragmentation, as shown by TUNEL assay. The activated form of caspase-3 (p17 cleaved form) was present in attached, viable macrophages before exposure to oxLDL. This p17 form was also found in apparently viable as well as in TUNEL-positive cells within atherosclerotic lesions of chow-fed apolipoprotein E-deficient (ApoE-/-) mice. The amount of p17 caspase-3 was reduced by in vitro blockade of FasL with an FasL-blocking antibody and was absent in macrophages from lpr/lpr mice, which lack functional Fas. Moreover, lpr/lpr macrophages resisted oxLDL cytotoxicity. The naturally occurring Fas-FasL induction of caspase-3 cleavage after macrophage attachment may represent an importa...Continue Reading

References

Jan 1, 1989·Free Radical Research Communications·H EsterbauerM Rotheneder
Mar 1, 1986·The Journal of Clinical Investigation·J W HeineckeA Chait
Jul 1, 1993·The International Journal of Biochemistry·P Greenspan, P Lou
May 17, 1996·The Journal of Biological Chemistry·M Lougheed, U P Steinbrecher
Jul 1, 1996·The Journal of Pathology·S J HardwickJ N Skepper
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S FazioM F Linton
Apr 21, 1997·The Journal of Experimental Medicine·P A KienerW C Liles
Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Apr 10, 1999·Methods : a Companion to Methods in Enzymology·J C Wu, L C Fritz
May 26, 1999·Cardiovascular Research·D E Gutstein, V Fuster
Dec 22, 1999·The Journal of Experimental Medicine·K B Elkon
Jan 12, 2000·Experimental & Molecular Medicine·C Y Han, Y K Pak
Feb 24, 2000·The Journal of Pathology·M M Kockx, M W Knaapen
May 3, 2000·The Journal of Biological Chemistry·P M Yao, I Tabas
Jun 16, 2000·Journal of Atherosclerosis and Thrombosis·H HakamataS Horiuchi
Feb 13, 2001·The Journal of Clinical Investigation·S FazioR V Farese
Feb 13, 2001·Atherosclerosis·J L Johnson, C L Jackson
Feb 24, 2001·The Journal of Experimental Medicine·Y ZermatiO Hermine
Mar 10, 2001·Cell·C K Glass, J L Witztum
Sep 19, 2001·Current Opinion in Lipidology·S R Panini, M S Sinensky
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Pasan FernandoLynn A Megeney

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Citations

Sep 14, 2004·Current Opinion in Lipidology·Urs P SteinbrecherVincent Duronio
Sep 3, 2008·Apoptosis : an International Journal on Programmed Cell Death·Susan MatuleviciusJames A de Lemos
Aug 29, 2006·The American Journal of Pathology·Thomas Q NhanStephen M Schwartz
May 13, 2014·Biochimica Et Biophysica Acta·Yinan Hua, Sreejayan Nair
Nov 30, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc C PulancoDeborah A Fraser
Feb 19, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Thomas Q NhanStephen M Schwartz
Sep 9, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Frank D KolodgieRenu Virmani
Jun 12, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Ken A LindstedtPetri T Kovanen
Feb 12, 2005·Circulation Research·David MorrowPaul A Cahill
Jan 25, 2007·The EMBO Journal·Richard FoxStephen M Schwartz
Sep 1, 2006·American Journal of Physiology. Cell Physiology·David MorrowPaul A Cahill
Jul 6, 2010·Chinese Medical Sciences Journal = Chung-kuo I Hsüeh K'o Hsüeh Tsa Chih·Jian-ling TaoXue-wang Li
Nov 17, 2016·Oxidative Medicine and Cellular Longevity·Mandy O J GrootaertWim Martinet
Feb 22, 2005·Current Opinion in Neurobiology·Michel MallatCyril Chéret

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