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Oxidation-dependent maturation and survival of explanted blood monocytes via Bcl-2 up-regulation

Authors
  • Cristofanon, Silvia
  • Nuccitelli, Silvia
  • D’Alessio, Maria
  • Dicato, Mario
  • Marc Diederich
  • Ghibelli, Lina
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Dec 24, 2008
Volume
76
Issue
11
Pages
1543–1543
Identifiers
DOI: 10.1016/j.bcp.2008.07.042
Source
LBMCC
Keywords
License
Green

Abstract

Monocytes isolated and cultured according to standard procedures from the blood of 22 healthy donors display an activation process, monitored as adhesion and increased exposure of CD11. Starting from very early time points, monocytes undergo a deep redox modulation, i.e., they increase reactive oxygen species (ROS) formation and decrease glutathione content; at the same time, the anti-apoptotic protein Bcl-2 is substantially up-regulated. The cause-effect relationship between these parameters was investigated. On the one side, pharmacological glutathione depletion with BSO further increases ROS formation and Bcl-2 levels. On the other side, scavenging of ROS by Trolox prevents Bcl-2 up-regulation. Two lipoxygenase (LOX) inhibitors (CAPE or AA861) prevent ROS increase and, accordingly, also prevent Bcl-2 up-regulation. All this evidence supports the redox-sensitivity of Bcl-2 regulation. Trolox, CAPE and AA861, i.e., all treatments that abolish ROS increase and prevent Bcl-2 up-regulation, increase the rate of cell loss, whereas BSO, increasing Bcl-2, reduces cell loss and induces chemo-resistance. Thus, explanted healthy monocytes seem to undergo an oxidation-dependent maturation implying increased survival via Bcl-2 up-regulation, perhaps mimicking physiological activation.

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