Abstract
Apoptosis is a process of programmed cell death which has an important role in tissue homeostasis and in the control of organism development. Here, we focus on information concerning the role of the extrinsic apoptotic pathway in the control of human erythropoiesis. We discuss the role of tumor necrosis factor α (TNFα), tumor necrosis factor ligand superfamily member 6 (FasL), tumor necrosis factor-related apoptosis-inducing (TRAIL) and caspases in normal erythroid maturation. We also attempt to initiate a discussion on the observations that mature erythrocytes contain most components of the receptor-dependent apoptotic pathway. Finally, we point to the role of the extrinsic apoptotic pathway in ineffective erythropoiesis of different types of β-thalassemia.
Highlights
Erythrocytes have a life span of approximately 120 days, at the end of which they become senescent and are removed from the circulation
The scrambling of membrane phospholipid asymmetric distribution and cell shrinkage caused by Ca2+ is enhanced by ceramide arising from sphingomyelin hydrolysis, which is another stimulus of eryptosis
The asymmetrical division of LT-hematopoietic stem cells (HSCs) gives rise to short-term repopulating HSCs (ST-HSCs), the asymmetrical division of which is the source of the multipotent progenitor cells (MPP-HSCs)
Summary
Erythrocytes have a life span of approximately 120 days, at the end of which they become senescent and are removed from the circulation. The extrinsic apoptotic pathway triggers apoptosis by the binding of ligands to death receptors, which leads to the formation of a death-inducing signaling complex (DISC) and, in consequence, caspases activation. These receptors are members of the tumor necrosis factor receptor superfamily (TNFRSF). In some cell lines, a second cytosolic complex is formed upon ligand stimulation This complex, called complex II, composed of FADD, procaspase-8 and c-FLIPs, might amplify caspase activation by processing caspase-3 (Figure 1a) [30]. Complex I dissociates from the death receptor and binds FADD and procaspase-8 (complex II), the activation of which leads to an induction of apoptosis (Figure 1c) (reviewed in [30]). Another study showed that RNF31 limits caspase-8 activity in complex I and complex II in TRAIL signaling, which causes inhibition of apoptosis [47,48]
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