Nucleotide Receptor P2X7 In Leukemic Cells

P2X7 receptor (previously referred to as the cytolytic receptor P2Z) is a novel ion channel, belonging to the P2X family, which consists of seven ionotropic ATP-gated channels (P2X1-P2X7) characterized by two transmembrane domains with both intracellular amino and carboxyl termini. P2X7 is distinct from other P2X receptors in terms of its longest C-terminal intracellular domain, pharmacology and ability to form cytolytic pores. Exposure to ATP or the more potent agonist BzATP renders P2X7 permeable to Na⁺, K⁺ and Ca²⁺, while repeated or prolonged application of either agonist induces the formation of a cytolytic pore, which is permeable to larger cations such as positively-charged ethidium, fluorescence yellow and YO-PRO-1. Opening of this pore leads to complete depolarization of the membrane potential and, ultimately, cell death. The nucleotide receptor P2X7 is widely expressed in hematopoietic cells. The physiological function of this receptor remains a subject of investigation, and a number of diverse activities have been proposed, including activation and maturation of T cells, formation of giant cells, killing of invading microorganisms in macrophages, and activation of various signaling cascades. The receptor also has been proposed to serve as a regulator of inflammation such as IL-1β, IFN-γ and TNF-a. It also induces cell proliferation, differentiation, and death through either necrosis or apoptosis.Recently, the high expression of P2X7 in B-cell subpopulation of progress B-cell chronic lymphocytic leukemia (B-CLL) was reported and it may correlate with severity of B-CLL. In order to study the characterizations and roles of P2X7 in hematopoietic cells especially in leukemia cells, we have completed the following works in this thesis:...