7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling

Cardiovascular Research
Cheikh I SeyeH Bult

Abstract

7-Ketocholesterol, a major oxysterol in oxidized low-density lipoproteins in advanced atherosclerotic plaques, induces vascular smooth muscle cell (SMC) death. We investigated whether cytochrome c release participated in SMC death induced by 7-ketocholesterol and whether the processes were reversible. SMC cultures derived from the rabbit aorta were exposed to 25 microM 7-ketocholesterol. Cytochrome c and Bax were studied by means of immunofluorescence and immunoblotting, apoptosis by the TUNEL technique and mitochondrial structure by transmission electron microscopy. 7-Ketocholesterol induced rapid upregulation of the proapoptotic protein Bax and its translocation from cytosol into the mitochondria (4 h). This was followed by mitochondrial cytochrome c release (65% at 8 h) into the cytosol, which was almost complete at 16 h. The mitochondria became spherical and ultracondensed, without showing signs of lysis. They clustered around the nucleus and were wrapped by wide cisternae of the rough endoplasmic reticulum. Cytochrome c release was not blocked by the pan-caspase inhibitor zVAD-fmk, in contrast to DNA fragmentation and SMC loss. Interestingly, upon removal of 7-ketocholesterol after 16 h and re-exposure to serum for 24 h, t...Continue Reading

Citations

Jul 5, 2005·Biochemical and Biophysical Research Communications·Hyun Sun LeeKoanhoi Kim
Jun 5, 2013·Cardiovascular Research·Avinash AppukuttanYury Ladilov
Sep 14, 2013·FEMS Yeast Research·Qiulin YueXin Zhang
Jul 26, 2005·Archives of Biochemistry and Biophysics·Rong TangKaixun Huang
May 8, 2007·The Journal of Biological Chemistry·Thanh H TranNanette H Bishopric
Oct 4, 2017·Lipids in Health and Disease·Adam Zmysłowski, Arkadiusz Szterk
Jan 14, 2020·Redox Biology·Amelia AndersonMatthew S O'Connor
Jan 17, 2008·Journal of Medicinal Chemistry·L MondragónE Pérez-Payá

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