Señal de calcio y oxidantes en la apoptosis de células leucémicas HL-60

Abstract

Apoptosis is a physiological process highly regulated which is associated with [Ca2+]I increase and ROS production, producing mitochondrial collapse and the release of pro-apoptotic mitochondrial factors, which eventually produce cell death. Tumor necrosis factor, TNF?, is a member of a group of cytokines that stimulate the acute phase reaction. The primary role of TNF is in the regulation of immune cells. TNF is able to induce apoptotic cell death and inflammation. Dysregulation of TNF production has been implicated in a variety of human diseases, as well as cancer. TNF-R1 is involved in death signaling. TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces its autoproteolytic activation and subsequent cleaving of effector caspases, leading to cell apoptosis. This would be an example of processes called as extrinsic pathway of apoptosis. Taken together, our objective is elucidating intracellular mechanisms involved in TNF-induced apoptosis, trying to analyse the contribution of mitochondria as ROS seed. Additionally, we will try to analyse the relationship between Ca2+ signaling and ROS, and the implication of endogenous production of ROS in TNF?-induced apoptosis. For this, we will use the HL-60 cell line, and we will compare them with K-562 and U937.