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A major ozonation product of cholesterol, 3β‐hydroxy‐5‐oxo‐5,6‐secocholestan‐6‐al, induces apoptosis in H9c2 cardiomyoblasts
Author(s) -
Sathishkumar K.,
Haque Masudul,
Perumal Thirugnanam E.,
Francis Joseph,
Uppu Rao M.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.044
Subject(s) - apoptosis , dna fragmentation , necrosis , chemistry , reactive oxygen species , phosphatidylserine , fragmentation (computing) , viability assay , cholesterol , programmed cell death , cytotoxicity , dna damage , microbiology and biotechnology , biochemistry , biology , membrane , medicine , dna , phospholipid , in vitro , ecology
Cholesterol, a major neutral lipid component of biological membranes and the lung epithelial lining fluids, is susceptible to oxidation by reactive oxygen and nitrogen species including ozone. The oxidation by ozone in biological environments results in the formation of 3β‐hydroxy‐5‐oxo‐5,6‐secocholestan‐6‐al (cholesterol secoaldehyde or CSeco, major product) along with some other minor products. Recently, CSeco has been implicated in the pathogenesis of atherosclerosis and Alzheimer's disease. In this communication, we report that CSeco induces cytotoxicity in H9c2 cardiomyoblasts with an IC 50 of 8.9 ± 1.29 μM ( n = 6). The observed effect of CSeco at low micromolar concentrations retained several key features of apoptosis, such as changes in nuclear morphology, phosphatidylserine externalization, DNA fragmentation, and caspase 3/7 activity. Treatment of cardiomyocytes with 5 μM CSeco for 24 h, for instance, resulted in 30.8 ± 3.28% apoptotic and 1.8 ± 1.11% of necrotic cells as against DMSO controls that only showed 1.3 ± 0.33% of apoptosis and 1.6 ± 0.67% of necrosis. In general, the loss of cellular viability paralleled the increased occurrence of apoptotic cells in various CSeco treatments. This study, for the first time, demonstrates the induction of apoptotic cell death in cardiomyocytes by a cholesterol ozonation product, implying a role for ozone in myocardial injury.