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Reactive oxygen and nitrogen species: efficient, selective, and interactive signals during intercellular induction of
1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79104 Freiburg, Germany. tgfb@.ukl.uni-freiburg.de
Abstract:
During intercellular induction of apoptosis, transformed fibroblasts are specifically eliminated by their nontransformed neighbours. This potential control step of oncogenesis is based on a sophisticated system of interdependencies and interactions of reactive oxygen and nitrogen species. Activated nontransformed effector cells release a novel peroxidase and nitric oxide. Superoxide anions generated extracellularly by transformed cells participate in intercellular signalling and also determine transformed cells as selective targets for intercellular induction of apoptosis. The interaction of these molecules results in two major signalling pathways, which are based on HOCl/hydroxyl radicals and on NO/peroxynitrite. In addition, involvement of nitrylchloride seems to be conceivable in an alternative pathway. Hydrogenperoxide plays a central and ambivalent role by fostering the HOCl/hydroxyl radical pathway and by inhibiting the NO/peroxynitrite pathway. The interaction of ROS and RNS during intercellular induction of apoptosis seems to represent a general signalling concept utilized by several natural antitumor systems.
Insights
Nontransformed cells eliminate cancerous ones via intercellular apoptosis, utilizing reactive oxygen and nitrogen species. This process involves specific signaling pathways crucial for natural anti-tumor defenses.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Intercellular apoptosis is a mechanism where normal cells eliminate transformed cells.
- This process is vital for controlling oncogenesis.
- Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are implicated in this elimination.
Purpose of the Study:
- To elucidate the molecular mechanisms of intercellular apoptosis induction.
- To identify the roles of specific ROS and RNS in targeting transformed cells.
- To understand the signaling pathways involved in this anti-tumor mechanism.
Main Methods:
- Investigated the interactions of reactive oxygen and nitrogen species during apoptosis induction.
- Identified novel peroxidase and nitric oxide released by effector cells.
- Analyzed extracellular superoxide anion involvement in transformed cell targeting.
Main Results:
- Transformed cells are selectively eliminated by nontransformed neighbors through apoptosis.
- Two major signaling pathways identified: HOCl/hydroxyl radicals and NO/peroxynitrite.
- Hydrogen peroxide plays a dual role, promoting one pathway and inhibiting another.
Conclusions:
- The interaction of ROS and RNS is central to intercellular apoptosis.
- This represents a general signaling concept in natural anti-tumor systems.
- Understanding these pathways could offer new strategies for cancer control.