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Role of Redox Controls of Caspase Activities in Regulation of Cell Death

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Abstract:

Caspases are a family of aspartate-specific cysteine proteinases that play a critical role in the execution phase of apoptosis. They are normally present in cells in a proenzyme form that requires limited proteolysis for enzymatic activity. The processing of caspases needs the reduction of a cysteine residue as well as other cysteine residues around the catalytic site for enzymatic activity and dimerization via sulfhydryl groups. Therefore, both processing and activity are inhibited in the presence of an excess of an oxidant such as hydrogen peroxide or nitric oxide and thiol-oxidizing agents, and enhanced in the presence of an anti-oxidant such as dithiothreitol or glutathione. On the other hand, reactive oxygen species (ROS) released from mitochondria decrease the concentration of cellular glutathione during apoptosis. Under physiological conditions, ROS are needed for survival. The redox valance decides the fate of cells, survival or death involving apoptosis and necrosis. In this review, we discussed the relationship between the redox control of caspase activity and cell death.

Keywords: apoptosis; caspase; necrosis; nitrosylation; oxidation; reactive oxygen species (ros)

Document Type: Review Article

DOI: https://doi.org/10.2174/157340805774580493

Affiliations: Laboratory of Radiation Biology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka-shi 422-8526, Japan.

Publication date: 2005-11-01

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  • Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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