Dynamics and mechanism of HSP70 translocation induced by photodynamic therapy treatment

Abstract

Heat shock protein 70 (HSP70) is involved in nearly all intracellular compartments. It has been recently shown to be expressed on the outer cellular membrane under photodynamic therapy (PDT) treatment. However, the mechanism and function of HSP70 translocation to the cell surface during PDT treatment are not well understood. In this study, the dynamics and mechanism of HSP70 translocation onto the cell surface and its relationship with several key intracellular events after PDT treatment were investigated using confocal microscopy. HeLa and ASTC-a-1 tumor cells were treated by PDT using different doses. In the case of PDT-induced apoptosis, cytoplasmic HSP70 rapidly translocated to the cell surface after treatment, but it was not released into the medium. Such translocation was found to be dependent on the PDT dose. Moreover, during apoptosis, the translocation of HSP70 was closely related to the changes of mitochondrial transmembrane potential (ΔΨm). Under non-lethal PDT induced surface stress, HSP70 also translocated to the cell surface, but with a slower rate and a lower final surface concentration. These findings reaffirm the HSP70 translocation onto the cell surface under PDT treatment in living cells. Our results also indicate that the function of the surface expression of HSP70, either initiated by mitochondrial disruption or direct surface stress, is to stabilize the plasma membrane integrity, although such function failed to prevent apoptosis induced by lethal PDT treatment, as evidenced in our study.