Paraptosis and Photodynamic Therapy: A Progress Report

Abstract

Abstract Photodamage to the endoplasmic reticulum (ER) can initiate a death pathway termed paraptosis. The “canonical” model of paraptosis, initiated by certain drugs and other stimuli, requires a brief interval of protein synthesis, involves the action of MAP kinases and can be followed by biochemical markers. The latter include changes in expression of AIP‐1/Alix and IGF‐1R proteins and translocation of HMGB‐1 from nucleus to plasma membrane. There is also a report indicating that an enhanced level of autophagy can impair death by paraptosis. The pathway to paraptosis follows the canonical pathway when ER photodamage is minor (<LD 50 ). When the extent of ER photodamage approaches LD 90 levels, there are deviations from the “canonical” pathway: interfering with protein synthesis does not prevent paraptosis nor does a brief chilling of cells after irradiation, MAP kinases are not involved, and stimulation of autophagy was not cytoprotective. We had previously speculated that ER protein cross‐linking might potentiate paraptosis (Photochem. Photobiol. 95, 2019, 1239) but this appears to be incorrect. At higher PDT doses, substantial cross‐linking of a typical ER protein (BiP, binding immunoglobin protein, an HSP chaperone) was detected and paraptosis was impaired. This may relate to decreased mobility of cross‐linked proteins. Other pathways to cell death were then observed.

Topics & Concepts