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. (C) 2008 Elsevier Inc. All rights reserved.

Cristofanon, S., Nuccitelli, S., D'Alessio, M., Dicato, M., Diederich, M., Ghibelli, L. (2008). Oxidation-dependent maturation and survival of explanted blood monocytes via Bcl-2 up-regulation. BIOCHEMICAL PHARMACOLOGY, 76(11), 1533-1543 [10.1016/j.bcp.2008.07.042].

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

GHIBELLI, LINA
2008-01-01

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. (C) 2008 Elsevier Inc. All rights reserved.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/13 - BIOLOGIA APPLICATA
English
Con Impact Factor ISI
BSO; Glutathione; Lipoxygenase; Reactive oxygen species; U937
Cristofanon, S., Nuccitelli, S., D'Alessio, M., Dicato, M., Diederich, M., Ghibelli, L. (2008). Oxidation-dependent maturation and survival of explanted blood monocytes via Bcl-2 up-regulation. BIOCHEMICAL PHARMACOLOGY, 76(11), 1533-1543 [10.1016/j.bcp.2008.07.042].
Cristofanon, S; Nuccitelli, S; D'Alessio, M; Dicato, M; Diederich, M; Ghibelli, L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/41544
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