Characterization of the progression of apoptosis triggered by the extrinsic pathway in vivo

• Main Authors: Chang-Feng Chu, 朱長風
• Other Authors: Ivan Dzhagalov
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/42950447520637161105

碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 104 === Apoptosis, a major form of programmed cell death, is important during the development and adult life. For example, it plays a crucial role during the development of T cells in the thymus by regulating their selection. We have established an experimental system to observe the dynamics of cell death and clearance during negative selection in the thymus that is triggered through the intrinsic pathway of apoptosis, and we wanted to compare our observations to the sequence of events during thymocytes cell death triggered by death receptor (Fas) ligation, which proceeds through the extrinsic pathway of apoptosis. We found that apoptosis proceeded through a similar time course regardless of whether the intrinsic or the extrinsic pathway was engaged: caspase 3 was first activated between two and three hours after the stimulation, followed by phosphatidylserine (PS) externalization and cell clearance. Caspase 3 was required for PS exposure and efficient clearance during FasL-triggered cell death, however blocking externalized PS did not reduce, but paradoxically accelerated cell loss and clearance. Thus, we have confirmed that apoptosis follows similar time line no matter which pathway is activated and we have defined the requirement for caspase 3 activation for cell clearance.