Homologous adaptation to oxidative stress induced by the photosensitized Pd-bacteriochlorophyll derivative (WST11) in cultured endothelial cells

Various forms of cellular stress induce adaptive responses through poorly understood mechanisms. In maintaining homeostasis, endothelial cells respond and adapt to changes in oxidative stress that prevail in the circulation. Endothelial cells are also the target of many oxidative stress-based vascular therapies. The objectives of this study were to determine whether endothelial cells adapt to oxidative stress induced upon the photosensitization of WST11 (a water-soluble Pd-bacteriochlorophyll derivative being developed as a photodynamic agent) and to study possible cellular mechanisms involved. The hallmark of WST11-based photodynamic therapy is the in situ generation of cytotoxic reactive oxygen species causing vascular shutdown, hypoxia, and tumor eradication. Here we demonstrated that photodynamic therapy also induces adaptive responses and tolerance following a sublethal preconditioning of endothelial cells with the same (homologous) or different (heterologous) stressor. A link among p38 MAPK activity, expression of hsp70 and hsp27, and homologous adaptation to reactive oxygen species induced by photosensitized WST11 was established. In addition to characterization of some key proteins involved, our observations provide a beneficial new working tool for the studies of mechanisms involved in oxidative stress and adaptation using light-controlled photosensitization.