Posted 10 July 2004 - 06:46 PM
Found more on this from Trends in Cell Biology:
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Despite the stereotyped view that caspases are chief executioners of cell death, there are several instances where caspase activation fails to trigger cell death. Somewhat paradoxically, deadly caspases play an important role at the beginning of life itself, during sperm formation in Drosophila. Caspases aid the process of sperm individualization, through which spermatids become separated from syncytia and lose the bulk of their cytoplasm [53]. During individualization, a cytoskeletal membrane complex, known as the individualization complex, translocates along spermatids, disconnecting cytoplasmic ‘bridges’ between them and expelling spermatid cytoplasm and unnecessary organelles into a membrane bag called the cystic bulge. Immunostaining for activated drice marked the pre-individualized part of the spermatid and the cystic bulge [53]. Indeed, the cystic bulge also stained with the apoptosis-associated marker acridine orange [53]. Synthetic and viral pan-caspase inhibitors severely impaired movement of the individualization complex and prevented removal of bulk cytoplasm from the spermatids [53]. It is not known how the activated caspase facilitates the movement of the individualization complex. It is also unclear whether caspases have a direct role in exclusion of cytoplasm from the spermatid, although it is reasonable to hypothesize that caspase activity might aid the degradation of expelled cytoplasm in the cystic bulge. The morphological defects and sterility of Drosophila sperm treated with caspase inhibitors strikingly resemble a common abnormality in human sperm; mouse knockouts of some apoptotic genes also cause male sterility [53]. Thus, although these mammalian defects are largely uncharacterized, they might also point to a non-lethal role of caspases.
In red blood cells and lens fiber cells, caspase activation leads to a subset of apoptotic morphological changes without causing cell death. As embryonic erythroid cells differentiate into adult red blood cells, they show signs of apoptosis, including chromatin compaction, nuclear destruction and caspase activation [54]. Yet, although the cytoplasm of an apoptotic cell contracts, that of a differentiating red blood cell expands [55]. Lens fiber cells develop from epithelial cells that degrade their organelles and nuclei during differentiation, presumably to allow cellular transparency. Caspases are expressed in developing lens fiber cells [56], and zVAD.fmk can reduce nuclear destruction in an in vitro model of rat lens-fiber differentiation [56]. In transgenic mice that overexpressed Bcl-xL, the lens fibers did not lose their nuclei [57]. In both of these cell examples, it is unclear how caspase activity is controlled to trigger only non-lethal aspects of the apoptotic program.
There are also examples of caspase activation promoting differentiation in the absence of any morphological signs of apoptosis. For example, during infection, human monocytes differentiate to form macrophages. The differentiation process does not show morphological features of apoptosis [58]; however, antibody staining showed caspase activation at the time of the switch; and the monocyte–macrophage switch was blocked by caspase inhibitors [58]. Caspase-8 might also play a role in differentiation because caspase-8 knockout mice exhibit defects in the development of heart muscle and also have a dramatically decreased pool of hematopoietic precursors [59]. These defects are not apparently related to abnormal cell death. The activity of human Caspase-14 was associated with the terminal differentiation of keratinocytes [60 and 61].
Immune functions are probably the best-characterized examples of non-lethal roles for caspases that do not involve apoptotic changes. Murine knockouts of caspase-1 [62 and 63] and caspase-11 [64] develop normally, apart from defects in the production of IL-1 and IL-1 in response to the bacterial compound lipopolysaccharide (LPS). A human family pedigree showed that caspase-8 mutations are linked to defects in the activation of T, B and NK cells [65]. Mice studies corroborated a role for caspase-8 in T-cell function, because a targeted caspase-8 deletion in T cells caused defects in activation-induced expansion of peripheral T cells, T-cell activation and the ability of T cells to clear lymphocyte choriomeningitis virus [66]. Interestingly, in addition to their immune functions, caspase-1, -8 and -11 can also promote apoptosis, because cells from mice harboring knockout alleles of these caspases have impaired death-receptor-mediated PCD [59, 63 and 67]. The link between caspases and the immune system also extends to Drosophila. A fly screen to identify mutants defective in innate immunity revealed that a mutant of the caspase Dredd mounted a defective immune response when challenged with Gram-negative
bacteria [17].
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Trends in Cell Biology
Volume 14, Issue 4 , 1 April 2004, Pages 184-193
doi:10.1016/j.tcb.2004.03.002
So, it does seem that this should be not too alarming for it to be present within ESCs.