Death by a Thousand Cuts: Granzyme Pathways of Programmed Cell Death

Dana Farber Cancer Institute and Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Annual Review of Immunology (Impact Factor: 39.33). 02/2008; 26(1):389-420. DOI: 10.1146/annurev.immunol.26.021607.090404
Source: PubMed


The granzymes are cell death-inducing enzymes, stored in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, that are released during granule exocytosis when a specific virus-infected or transformed target cell is marked for elimination. Recent work suggests that this homologous family of serine esterases can activate at least three distinct pathways of cell death. This redundancy likely evolved to provide protection against pathogens and tumors with diverse strategies for evading cell death. This review discusses what is known about granzyme-mediated pathways of cell death as well as recent studies that implicate granzymes in immune regulation and extracellular proteolytic functions in inflammation.

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Available from: Dipanjan Chowdhury, Aug 06, 2015
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    • "Impaired mitochondrial function and deranged metabolism in the liver of rats exposed to PVB was restored by melatonin. The antioxidant effects of melatonin have been well described, and are known to include both direct and indirect effects with equal efficiency in nucleus, cytosol, and mitochondria of the cell (Chowdhury and Lieberman, 2008). It scavenges a variety of free radicals and ROS, such as hydroxyl radical (Tan et al., 2007), peroxy radical (Pieri et al., '94), nitric oxide (Tan et al., 2007), hydrogen peroxide (Barlow-Walden et al., '95), and singlet oxygen (Cagnoli et al. '95) and also up regulates certain antioxidant enzymes like SOD, catalase and glutathione peroxidise (Barlow-Walden et al., '95; Liu and Ng, 2000; Rodriguez et al., 2004; Reiter et al., 2006; Tan et al., 2007). "
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    • "In contrast to what is suggested in relation with APC cells, a significant increase in the recruitment of cytotoxic cells, according to the expression levels of cytotoxic T and NK cell peptides granzyme (Chowdhury and Lieberman, 2008) and NK lysin (Andersson et al., 1995), in response to the expression of zfBD2 was detected in the muscle of fish injected with pMCV1.4-zfBD2 (Fig. 2C) compared to both control and pMCV1.4-injected "

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    • "Secretory lysosomes are polarized towards the immunological synapse, where they fuse with the plasma membrane releasing their cytotoxic contents [4]–[6]. The pore forming protein perforin then facilitates the entry of pro-apoptopic granzymes into the target cell cytoplasm resulting in cell death [2], [3]. "
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