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Target Concepts:
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Query: UNIPROT:Q8IXL6 (
RNS
)
1,091
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nitrite and H
2
O
2
are long-lived species in cold atmospheric plasma and plasma-activated medium. It is known that their synergistic interaction is required for selective apoptosis induction in tumor cells that are treated with plasma-activated medium. This study shows that the interaction between nitrite and H
2
O
2
leads to the formation of peroxynitrite, followed by singlet oxygen generation through the interaction between peroxynitrite and residual H
2
O
2
. This primary singlet oxygen causes local inactivation of few catalase molecules on the surface of tumor cells. As a consequence, H
2
O
2
and peroxynitrite that are constantly produced by tumor cells and are usually decomposed by their protective membrane-associated catalase, are surviving at the site of locally inactivated catalase. This leads to the generation of secondary singlet oxygen through the interaction between tumor cell-derived H
2
O
2
and peroxynitrite. This selfsustained process leads to autoamplification of secondary singlet oxygen generation and catalase inactivation. Inactivation of catalase allows the influx of H
2
O
2
through aquaporins, leading to intracellular glutathione depletion and sensitization of the cells for apoptosis induction through lipid peroxidation. It also allows to establish intercellular apoptosis-inducing HOCl signaling, driven by active NOX1 and finalized by lipid peroxidation through hydroxyl radicals that activates the mitochondrial pathway of apoptosis. This experimentally established model is based on a triggering function of CAP and
PAM
-derived H
2
O
2
/nitrite that causes selective cell death in tumor cells based on their own ROS and
RNS
. This model explains the selectivity of CAP and
PAM
action towards tumor cells and is in contradiction to previous models that implicated that ROS/
RNS
from CAP or
PAM
were sufficient to directly cause cell death of tumor cells.
...
PMID:The synergistic effect between hydrogen peroxide and nitrite, two long-lived molecular species from cold atmospheric plasma, triggers tumor cells to induce their own cell death. 3142 9
Treatment of tumor cells with H
2
O
2
and nitrite, two long-lived species derived from cold atmospheric plasma, induces a complex autoamplificatory, singlet oxygen-mediated process, which leads to catalase inactivation and reactivation of intercellular apoptosis-inducing signaling. Experimental dissection and quantification of this process is described in this study. When tumor cells were pretreated with H
2
O
2
and nitrite, and then were added to untreated tumor cells, they propaged singlet oxygen mediated catalase inactivation and generation of singlet oxygen to the untreated cell population. This bystander effect allowed to analyze the biochemical requirements of a) induction of the bystander effect-inducing potential, b) transmission of the bystander effect to untreated neighbouring cells, and c) the biochemical consequences of these signaling events. The induction of bystander effect-inducing potential requires the generation of "primary singlet oxygen" through the reactions following the interaction between nitrite and H
2
O
2
, followed by local inactivation of a few catalase molecules. This primary effect seems to be very rare, but is efficiently enhanced by the generation of "secondary singlet oxygen" through the interaction between H
2
O
2
and peroxynitrite at the site of inactivated catalase. Transmission of bystander signaling between pretreated and untreated tumor cells depends on the generation of secondary singlet oxygen by the pretreated cells and singlet oxygen-mediated catalase inactivation of the untreated recipient cells. This induces autoamplificatory propagation of secondary singlet oxygen generation in the population. This experimental approach allowed to quantify the efficiencies of primary and secondary singlet oxgen generation after CAP and
PAM
action, to dissect the system and to study the underlying chemical biology in detail. Our data confirm that CAP and
PAM
-derived components are merely the trigger for the activation of autoamplificatory mechanisms of tumor cells, whereas the tumor cells efficiently propagate their cell death through their own ROS/
RNS
signaling potential.
...
PMID:Intercellular singlet oxygen-mediated bystander signaling triggered by long-lived species of cold atmospheric plasma and plasma-activated medium. 3144 12
