Execution of Apoptosis: Converging or Diverging Pathways?
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Pierluigi Nicotera
Abstract
There is increasing evidence that apoptosis and necrosis represent only two of several possible ways for cells to die. These two types of demise can occur simultaneously in tissues or cell cultures exposed to the same stimulus, and often local metabolic conditions and the intensity of the same initial insult decide the prevalence of either apoptosis or necrosis. Recent work has shown that execution of the apoptotic programme involves a relatively limited number of pathways. According to a general view, these would converge to activate the caspase family of proteases. However, there is increasing evidence that apoptotic-like features can be observed also in cells where caspases are inhibited by cell-permeable tripeptides, such as z-VaD-Ala-Asp-fluoromethyl ketone (z-VAD-fmk), or analogous compounds. This has posed the question as to whether apoptosis may or may not occur in a caspase independent way, and whether caspase inhibitors may be effective in the treatment of disease. Also relevant is the understanding that low intracellular energy levels during apoptosis can preclude caspase activation, and consequently decide the occurrence and mode of demise in damaged cells. In vivo, incomplete execution of damaged cells by apoptosis may have profound implications, as their persistence within a tissue, followed by delayed lysis, may elicit delayed pro-inflammatory reactions. In this minireview, we discuss some recent findings suggesting that cells may use diverging execution pathways, with different implications in pathology and therapy.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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- The Role of Protein Phosphatase 2A Catalytic Subunit Cα in Embryogenesis: Evidence from Sequence Analysis and Localization Studies
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Articles in the same Issue
- Execution of Apoptosis: Converging or Diverging Pathways?
- Two Highly Related Homeodomain Proteins, Nkx5-1 and Nkx5-2, Display Different DNA Binding Specificities
- The Janus Face of the Archaeal Cdc48/p97 Homologue VAT: Protein Folding versus Unfolding
- Functional Characterization of an Extremely Thermophilic ATPase in Membranes of the Crenarchaeon Acidianus ambivalens
- On the Lysosomal Degradation of Neurofibromin and Its Phosphorylation in Cultured Melanocytes
- Rat Muscle Fructose-1,6-Bisphosphatase: Cloning of the cDNA, Expression of the Recombinant Enzyme, and Expression Analysis in Different Tissues
- Catalase-Peroxidase from the Cyanobacterium Synechocystis PCC 6803: Cloning, Overexpression in Escherichia coli, and Kinetic Characterization
- Expression of Plasma Prekallikrein mRNA in Human Nonhepatic Tissues and Cell Lineages Suggests Special Local Functions of the Enzyme
- Biochemical Characterization of the Catalytic Domain of Membrane-Type 4 Matrix Metalloproteinase
- Fluorometric Microassays for the Determination of Cathepsin L and Cathepsin S Activities in Tissue Extracts
- The Role of Protein Phosphatase 2A Catalytic Subunit Cα in Embryogenesis: Evidence from Sequence Analysis and Localization Studies
- DNA Binding of Myc/Max/Mad Network Complexes to Oligonucleotides Containing Two E Box Elements: c-Myc/Max Heterodimers Do Not Bind DNA Cooperatively
- Tight Interaction between Densely Methylated DNA Fragments and the Methyl-CpG Binding Domain of the Rat MeCP2 Protein Attached to a Solid Support
- Molecular Characterization of a Novel Mammalian DnaJ-Like Sec63p Homolog
