Turning point in apoptosis/necrosis induced by hydrogen peroxide

Abstract

The turning point between apoptosis and necrosis induced by hydrogen peroxide (H2O2) have been investigated using human T-lymphoma Jurkat cells. Cells treated with 50 microM H2O2 exhibited caspase-9 and caspase-3 activation, finally leading to apoptotic cell death. Treatment with 500 microM H2O2 did not exhibit caspase activation and changed the mode of death to necrosis. On the other hand, the release of cytochrome c from the mitochondria was observed under both conditions. Treatment with 500 microM H2O2, but not with 50 microM H2O2, caused a marked decrease in the intracellular ATP level; this is essential for apoptosome formation. H2O2-reducing enzymes such as cellular glutathione peroxidase (cGPx) and catalase, which are important for the activation of caspases, were active under the 500 microM H2O2 condition. Prevention of intracellular ATP loss, which did not influence cytochrome c release, significantly activated caspases, changing the mode of cell death from necrosis to apoptosis. These results suggest that ATP-dependent apoptosome formation determines whether H2O2-induced cell death is due to apoptosis or necrosis.

Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte–dendritic cell cross-talk

“…H2O2 and heat shock are alternative treatments to induce tumour cell death. Hydrogen peroxide induces apoptosis via the caspase activation or necrosis by decreasing intracellular adenosine triphosphate (ATP) [30], while heat shock is known to favour HSP70 expression, a molecule involved in DC maturation and cross-presentation [10,[31][32][33][34]. Our results show that H2O2 plus heat shock succeeded in inducing necrosis of RCC cells.…”

Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo

“…A great deal of emerging evidence suggests that ROS are crucial mediators in intracellular signaling, including the Toll-like receptor signaling pathway, and ROS scavenging or NOX inhibition suppresses LPS-induced cytokine production (Bonizzi et al, 1999;Davies et al, 1999;Lee et al, 1999;Aslan et al, 2003;Tonks et al, 2005;Nakahira et al, 2006;Saito et al, 2006). However, the sources of ROS after the administration of these stimuli remain largely unknown.…”

“…Among these, the NADPH-oxidases (NOX) and cyclooxygenases / lipoxygenases are generally recognized as the principal physiological sources of O2 -, which is in turn dismutated into H2O2 (Babior et al, 1999;Griendling et al, 1999;Van Heerebeek et al, 2002;Kuhn et al, 1999;Rhee et al, 2003). H2O2 is now generally believed to be one of the most important ROS molecules in the modulation of multiple cellular events, including receptor-mediated signaling, apoptosis, proinflammation, and metabolism (Davies et al, 1999;Lee et al, 1999;Aslan et al, 2003;Tonks et al, 2005;Saito et al, 2006). Although the sources of ROS generated after stimulation with proinflammatory cytokines such as TNF-α and IL-1β remain to be clearly elucidated, several reports have indicated that 5-lipoxygenase (5-LOX) activity may be critically related to intracellular ROS production (Los et al, 1995;Lee et al, 1997).…”

Expression profiles of two small heat shock proteins and antioxidant enzyme activity in Mytilus galloprovincialis exposed to cadmium at environmentally relevant concentrations

“…Vertical bars represent the means±SE ( n =6). * Signifi cant differences ( P <0.05) and ** highly signifi cant differences ( P <0.01 (Saito et al, 2006). Relatively higher GPx activity might lead to lower GSH levels in the 5 μg/L Cd…”

“…-groups compared with that in 50 μg/L Cd 2+ -groups (Saito et al, 2006), which could explain the relatively higher sHsps in the 50 μg/L Cd-groups (Kannan et al, 2001). In addition, this phenomenon was in line with the inverted U-shaped model (a low dose of stimulation and high dose of inhibition) in toxicology (Calabrese, 2003;Calabrese, 2004 …”