A role for reactive oxygen species in endothelial cell anoikis

Arthur E. Li, Hideaki Ito, Ilsa I. Rovira, Kyung Soo Kim, Kazuyo Takeda, Zu Yi Yu, Victor J. Ferrans, Toren Finkel

Research output: Contribution to journalArticle

Abstract

When adherent cells, such as epithelial or endothelial cells, are detached and continuously maintained in suspension, they undergo a form of programmed cell death termed anoikis. We demonstrate that coincident with endothelial cell detachment, there is a dramatic rise in the intracellular level of reactive oxygen species (ROS). Reattachment to a solid surface rapidly attenuates the level of ROS. The mitochondria appear to be the major source of the detachment-induced rise in ROS. The change in the intracellular redox state appears to contribute to endothelial anoikis, because treatment with either the cell-permeant antioxidant N-acetylcysteine or the flavin protein inhibitor diphenylene iodonium is demonstrated to reduce oxidant levels and protect against subsequent cell death. Similarly, the endogenous intracellular level of ROS is shown to correlate with the extent of cell death. Finally, we demonstrate that the activities of both caspases and of the c-Jun N-terminal kinases are modulated by the rise in intracellular ROS levels. These results suggest that oxidants serve as signaling molecules and regulators of anoikis.

Original languageEnglish (US)
Pages (from-to)304-310
Number of pages7
JournalCirculation Research
Volume85
Issue number4
StatePublished - Aug 20 1999
Externally publishedYes

Fingerprint

Anoikis
Reactive Oxygen Species
Endothelial Cells
Cell Death
Oxidants
JNK Mitogen-Activated Protein Kinases
Acetylcysteine
Caspases
Oxidation-Reduction
Suspensions
Mitochondria
Antioxidants
Epithelial Cells
Proteins

Keywords

  • Caspase
  • Hydrogen peroxide
  • JNK
  • Mitochondria

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Li, A. E., Ito, H., Rovira, I. I., Kim, K. S., Takeda, K., Yu, Z. Y., ... Finkel, T. (1999). A role for reactive oxygen species in endothelial cell anoikis. Circulation Research, 85(4), 304-310.

A role for reactive oxygen species in endothelial cell anoikis. / Li, Arthur E.; Ito, Hideaki; Rovira, Ilsa I.; Kim, Kyung Soo; Takeda, Kazuyo; Yu, Zu Yi; Ferrans, Victor J.; Finkel, Toren.

In: Circulation Research, Vol. 85, No. 4, 20.08.1999, p. 304-310.

Research output: Contribution to journalArticle

Li, AE, Ito, H, Rovira, II, Kim, KS, Takeda, K, Yu, ZY, Ferrans, VJ & Finkel, T 1999, 'A role for reactive oxygen species in endothelial cell anoikis', Circulation Research, vol. 85, no. 4, pp. 304-310.
Li AE, Ito H, Rovira II, Kim KS, Takeda K, Yu ZY et al. A role for reactive oxygen species in endothelial cell anoikis. Circulation Research. 1999 Aug 20;85(4):304-310.
Li, Arthur E. ; Ito, Hideaki ; Rovira, Ilsa I. ; Kim, Kyung Soo ; Takeda, Kazuyo ; Yu, Zu Yi ; Ferrans, Victor J. ; Finkel, Toren. / A role for reactive oxygen species in endothelial cell anoikis. In: Circulation Research. 1999 ; Vol. 85, No. 4. pp. 304-310.
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