A major ozonation product of cholesterol, 3β-hydroxy-5-oxo-5,6- secocholestan-6-al, induces apoptosis in H9c2 cardiomyoblasts

K. Sathishkumar, Masudul Haque, Thirugnanam E. Perumal, Joseph Francis, Rao M. Uppu

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 IC50 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.

Original languageEnglish (US)
Pages (from-to)6444-6450
Number of pages7
JournalFEBS Letters
Volume579
Issue number28
DOIs
StatePublished - Nov 21 2005
Externally publishedYes

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Ozonization
Ozone
Cholesterol
Apoptosis
Cardiac Myocytes
Biological membranes
Caspase 7
Reactive Nitrogen Species
Oxidation
Phosphatidylserines
DNA Fragmentation
Cell death
Cytotoxicity
Dimethyl Sulfoxide
Linings
Caspase 3
Inhibitory Concentration 50
Reactive Oxygen Species
Atherosclerosis
Alzheimer Disease

Keywords

  • Apoptosis
  • Cardiomyocyte
  • Cholesterol secoaldehyde
  • Ozone

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A major ozonation product of cholesterol, 3β-hydroxy-5-oxo-5,6- secocholestan-6-al, induces apoptosis in H9c2 cardiomyoblasts. / Sathishkumar, K.; Haque, Masudul; Perumal, Thirugnanam E.; Francis, Joseph; Uppu, Rao M.

In: FEBS Letters, Vol. 579, No. 28, 21.11.2005, p. 6444-6450.

Research output: Contribution to journalArticle

Sathishkumar, K. ; Haque, Masudul ; Perumal, Thirugnanam E. ; Francis, Joseph ; Uppu, Rao M. / A major ozonation product of cholesterol, 3β-hydroxy-5-oxo-5,6- secocholestan-6-al, induces apoptosis in H9c2 cardiomyoblasts. In: FEBS Letters. 2005 ; Vol. 579, No. 28. pp. 6444-6450.
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