REACTIVE OXYGEN SPECIES INDUCE APOPTOSIS OF SYNOVIOCYTES IN VITRO. α-TOCOPHEROL PROVIDES NO PROTECTION

Authors

  • S. Galleron,

    1. Laboratoire de Biochimie, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
    2. Laboratoire de Pharmacologie, CNRS UPRES A 8068, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
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  • D. Borderie,

    1. Laboratoire de Biochimie, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
    2. Laboratoire de Pharmacologie, CNRS UPRES A 8068, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
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  • Ch Ponteziere,

    1. Laboratoire Central de Biologie, Hôpital Corentin Celton, 92133, Issy les Moulineaux Cedex, France
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  • H. Lemarechal,

    1. Laboratoire de Biochimie, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
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  • M. Jambou,

    1. Laboratoire Central de Biologie, Hôpital Corentin Celton, 92133, Issy les Moulineaux Cedex, France
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  • M. Roch-Arveiller,

    1. Laboratoire de Pharmacologie, CNRS UPRES A 8068, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
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  • O.G Ekindjian,

    1. Laboratoire de Biochimie, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
    2. Laboratoire de Pharmacologie, CNRS UPRES A 8068, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
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  • M.J Cals

    Corresponding author
    1. Laboratoire Central de Biologie, Hôpital Corentin Celton, 92133, Issy les Moulineaux Cedex, France
    2. Laboratoire de Pharmacologie, CNRS UPRES A 8068, Hôpital Cochin, 27 Rue du Faubourg St Jacques, 75679, Paris Cedex 14, France
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To whom correspondence should be addressed.

Abstract

Reactive oxygen species (ROS) are released during the inflammation of the synovial membrane associated with cartilage degradation in osteoarthritis. In this work, we exposed synoviocytes to superoxide anions at concentrations that may cause either apoptosis or necrosis. We studied membrane organization, dehydrogenase mitochondrial activity and nuclear morphology and integrity, to determine the nature of the death process initiated by superoxide anions and tried to counteract ROS effects with α-tocopherol. We found that oxidative stress caused synoviocytes to undergo a process of cell death of an apoptotic nature rather than necrotic. Mitochondrial injury occurred at an early stage, and the FITC-annexin-V-positive/propidium iodide-positive cells occurred later than the metabolic changes. DNA strand breaks were evident at 8h and nuclear condensation at 24h. No LDH activity was detected in culture supernatants. In our experimental conditions, α-tocopherol had little effect on stress damage; the antioxidant properties of this molecule did not affect the apoptosis caused by superoxide anions.

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