Hydrogen peroxide produced inside mitochondria takes part in cell-to-cell transmission of apoptotic signal

Abstract

In monolayer of HeLa cells treated with tumor necrosis factor (TNF), apoptotic cells formed clusters indicating possible transmission of apoptotic signal via the culture media. To investigate this phenomenon, a simple method of enabling two cell cultures to interact has been employed. Two coverslips were placed side by side in a Petri dish, one coverslip covered with apoptogen-treated cells (the inducer) and another with non-treated cells (the recipient). TNF, staurosporine, or H2O2 treatment of the inducer cells is shown to initiate apoptosis on the recipient coverslip. This effect is increased by a catalase inhibitor aminotriazole and is arrested by addition of catalase or by pre-treatment of either the inducer or the recipient cells with nanomolar concentrations of mitochondria-targeted cationic antioxidant MitoQ (10-(6 -ubiquinolyl)decyltriphenylphosphonium), which specifically arrests H2O2-induced apoptosis. The action of MitoQ is abolished by an uncoupler preventing accumulation of MitoQ in mitochondria. It is concluded that reactive oxygen species (ROS) produced by mitochondria in the apoptotic cells initiate the release of H2O2 from these cells. The H2O2 released is employed as a long-distance cell suicide messenger. In processing of such a signal by the recipient cells, mitochondrial ROS production is also involved. It is suggested that the described phenomenon may be involved in expansion of the apoptotic region around a damaged part of the tissue during heart attack or stroke as well as in "organoptosis", i.e. disappearance of organs during ontogenesis.

Alterations in antioxidant system, mitochondrial biogenesis and autophagy in preeclamptic myometrium

“…We support the hypothesis about influence on maternal organism through extracellular messengers such as ROS, e.g. in the form of hydrogen peroxide [29], [30], lipid peroxides, also calcium [31], microparticles (exosomes and microvesicles) [32], [33] and cytokines circulating in the blood of the mother and fetus [10], [32], [34], [35]. The alterations in protein expression levels observed in preeclamptic myometrium, may be due to the activity of agents derived from the placenta or proinflammatory factors.…”

Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress

“…For the same reason, H 2 O 2 added to a cell culture is quickly decomposed due to activity of catalase and other cellular H 2 O 2 -consuming systems. For example, we found that 20 μM H 2 O 2 added to a culture of HeLa cells was completely decomposed in 15-20 min [19]. On the other hand, significant accumulation of ROS in the H 2 O 2 -treated cells was detected 45 min after addition of peroxide (Fig.…”

Effect of dopamine on rat diaphragm apoptosis and muscle performance

“…Oxidants can often alter Ca 2+ release from the sarcoplasmic reticulum and can compromise excitation–contraction coupling in the diaphragm (Darnley et al 2001). Several investigators have demonstrated that apoptosis can be evoked when ROS‐induced mitochondria initiate the release of oxidants from the cells (Adhihetty et al 2005; Pletjushkina et al 2006; Valencia & Kochevar, 2006). In addition, other investigators have found that low intracellular partial pressure of O 2 induces a burst of oxidants, and that antioxidants have a protective influence on muscle function (Wright et al 2005; Zuo & Clanton, 2005).…”