Jeff hilliard synergy labs courier9/13/2023 ![]() ![]() This is evident by the fact that 95% of double positive (i.e., CD4/CD8) thymocytes undergo apoptosis as a consequence of negative selection ( Starr et al. Immature T cells are an ideal model for investigating apoptosis because they are programmed to die during development. Much that is known about calcium signaling came from immunological studies using activated lymphocytes ( Berridge 1997). The following sections provide a more detailed explanation of the varied ways in which calcium signals induce cell death and are themselves regulated.ĪPOPTOSIS REGULATION BY ANTIGEN RECEPTORS: A MODEL FOR PROGRAMMED CELL DEATH As discussed later in this review, calpains are reported to directly activate caspases, thus promoting apoptotic cell death independent of mitochondrial cytochrome c release. Another class of cysteine proteases, calpains, require calcium for their activation and are important mediators of apoptosis following ER stress. Caspases comprise a family of cysteine proteases that are essential for the classically observed cellular and biochemical characteristics of apoptosis, which include (but are not limited to) membrane blebbing, chromatin condensation, and DNA fragmentation. In brief, cytochrome c release stimulates apoptosis via its interaction with the protein Apaf-1, which in turn activates the initiator caspase-9 and the executioner caspase-3 ( Green 2005). In this review, we primarily focus our attention on the intrinsic pathway due to the importance of intracellular calcium in the regulation of this process. There are two conventional apoptosis pathways: the extrinsic pathway, which is typically initiated by death receptors (e.g., Fas) on the plasma membrane and the intrinsic (mitochondrial) pathway, which involves permeabilization of the outer mitochondrial membrane followed by the release of cytochrome c. For example, it is the primary mechanism by which potentially autoreactive T cells are eliminated from the immune system. It is required to maintain normal cell homeostasis or to eliminate a population of cells that may be harmful to the organism or unnecessary during organ development ( Green 2003). ![]() Apoptosis is a process of programmed cell death or suicide that occurs when cells have undergone irreversible stress or damage. ![]()
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