Mechanism of mitochondrial 7A6 antigen exposure triggered by distinct apoptotic pathways: Involvement of caspases

Abstract

During the early stages of apoptosis, 7A6 antigen is exposed on mitochondria. 7A6 antigen is observed in various cells and is thought to be a specific marker of apoptosis determination. However, the exposure mechanism of 7A6 during apoptosis is poorly understood. In this study, we used two major distinct (mitochondria-mediated and receptor-mediated) apoptotic pathways to elucidate the 7A6 exposure pathway. Jurkat cells were incubated with either a mitochondrial permeability transition pore open reagent FTY720, or anti-Fas antibody. 7A6 exposure was detected with a specific antibody, Apo2.7. Other apoptosis phenomena, including DNA fragmentation, caspase activation, and mitochondrial membrane potential decreases, were also observed to explore the correlation with 7A6 exposure. Both FTY720 and anti-Fas antibody were found to activate caspase-3 and exposed 7A6, to subsequently fragment DNA. Mitochondrial membrane potential decrease did not correlate to 7A6 exposure. When mitochondrial dysfunction was inhibited by the overexpression of Bcl-2, FTY720-induced 7A6 exposure was blocked, whereas 7A6 was still exposed in anti-Fas antibody treatment. Caspase inhibitor attenuated 7A6 exposure in both apoptotic pathways, suggesting that 7A6 exposure on mitochondria is a downstream effect of caspase activation. 7A6 antigen is exposed in a caspase-dependent manner. 7A6 exposure does not require mitochondrial perturbation.