ABSTRACT
Transforming growth factor (TGF)-beta pretreated nontransformed fibroblasts induce apoptosis selectively in transformed fibroblasts. This potential control step during oncogenesis has been termed intercellular induction of apoptosis. Selectivity and efficiency of intercellular induction of apoptosis depend on transformed target cell-derived superoxide anions that drive two intercellular signaling pathways--the HOCl/hydroxyl radical and the nitric oxide (NO)/peroxynitrite pathway. Other natural antitumor systems like macrophages or cells of the granulocyte lineage seem to utilize the same signaling chemistry. Our data demonstrate the existence of an alternative signaling pathway in these systems. This pathway depends on the presence of nitrite and is still effective when the two conventional signaling pathways are blocked by superoxide dismutase (SOD). Nitrite-dependent apoptosis induction is neither blocked by SOD nor by the hydroxyl radical scavenger terephthalate, but it is inhibited by the peroxidase inhibitor aminobenzoyl hydrazide and by the hypochlorous acid (HOCl) scavenger taurine. Therefore, nitrite, that is nontoxic for our cells, seems to interact with HOCl to form the apoptosis inducer nitryl chloride. Nitryl chloride-mediated apoptosis induction might be relevant for apoptosis induction in tumor cells that release SOD and thus escape the two classical signaling pathways.
Subject(s)
Apoptosis/physiology , Hypochlorous Acid/metabolism , Nitrites/metabolism , Signal Transduction/physiology , Superoxide Dismutase/metabolism , Animals , Apoptosis/drug effects , Cell Line, Transformed/cytology , Cell Line, Transformed/drug effects , Cell Line, Transformed/metabolism , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Coculture Techniques/methods , Fibroblasts/cytology , Fibroblasts/physiology , HL-60 Cells/cytology , Humans , Hydroxyl Radical/metabolism , Macrophages/cytology , Mice , Nitrates/metabolism , Nitric Oxide/metabolism , Nitrites/pharmacology , Rats , Signal Transduction/drug effects , Superoxide Dismutase/pharmacology , Superoxides/metabolism , Transforming Growth Factor beta/pharmacologyABSTRACT
Seeing the systemic aspects of the developmental and behavioral problems of young children, it has often been demanded, but is seldom realized, to include families, in early education. Though the role of parents has changed from passive observers to active partners of their child and the professionals the complete dimensions of this change of influence concerning all the family are still unknown. Hence the family is seldomly borne in mind, in practice as well as in research on early education. To answer some of the standing questions, a recourse to family stre beta theory, life span developmental theory, and ecological developmental psychology seems necessary. In every day life mainly the mothers seem to carry the burdon and concern of education and development of their children. On this presupposition we are convinced that mothers can give valuable informations about their family lives and family systems. Hypotheses concern the subjective changes of their families and their personal development during one year of early education and family related counseling. Comparisons between mothers with or without family counseling show important differences in developmental stress, developmental attitudes, and family dynamics. These findings are discussed considering to the limited evidence of practice attendant studies.
