The programmed cell death – apoptosis plays an important role in the life of the nucleated cells. It is a vital component of different processes, like normal cell cycle, embryonic development, development and functioning of the immune system, etc.  There are at least two signalling pathways that lead to apoptosis of the nucleated cells – the extrinsic pathway of the apoptosis and the intrinsic pathway of the apoptosis. The extrinsic pathway of apoptosis begins outside a cell, when conditions in the extracellular environment determine that a cell must die. The intrinsic pathway of apoptosis begins when an injury occurs within the cell and the resulting stress activates the apoptotic pathway. Erythrocytes, like nucleated cells, may undergo a form of suicidal cell death called eryptosis.  The fact is that erythrocytes, which are devoid of nuclei, contain most components of the receptor-dependent apoptotic pathway. The components of the extrinsic and intrinsic apoptotic pathways play a significant role at the different stages of erythropoiesis and even in mature erythrocytes. Mature erythrocytes contain most components of the receptor-dependent apoptotic pathway, however, common inducers of apoptosis do not activate this pathway.  Studies based on an animal model suggested that other stimuli, such as ROS or cholesterol accumulation, could activate the extrinsic apoptotic pathway. The data also demonstrate important effects of caspases-8 and caspase-3 on red cell membrane and membrane skeleton proteins, which are crucial in determining cell shape and erythrocyte deformability and therefore erythrocyte survival in the circulation. Understanding all of these processes may help to explain the pathophysiology of anemia. Despite extensive research, it is still unclear what the direct mechanism of apoptosis of erythroid cells is. 


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