Light and death: photons and apoptosis

Phototherapies like photodynamic therapy (PDT), UVA1, UVB, and PUVA treat skin diseases. These phototherapies work because they alter cytokine profiles, change immune cytotoxicity in the skin, and directly kill diseased cells by apoptosis. Apoptosis is a term that only describes the morphologic changes a cell undergoes during this mode of cell death. The terms "immediate", "intermediate", and "delayed" apoptosis segregate the different apoptotic mechanisms into three kinetic categories, whereas the terms preprogrammed cell death (pre-PCD) and programmed cell death (PCD) describe the underlying mechanisms. Immediate apoptosis (T< or =0.5 h post-exposure) is triggered by singlet-oxygen damage that opens the mitochondrial megachannel, which can be mediated by PDT or UVA1 radiation. It is a pre-PCD mechanism of apoptosis, i.e., protein synthesis is not required post-insult, because all the necessary components are constitutively synthesized and only need to be activated. Intermediate apoptosis (T< or =4 h>0.5 h) is initiated by receptor cross-linking on the plasma membrane, which can be achieved using high doses of UVB or UVC radiation. It is also a pre-PCD mechanism. Delayed apoptosis (T>4 h) is induced by DNA damage that can be caused by X-rays, PUVA, UVC, UVB, UVA, and PDT. It is a PCD mechanism of apoptosis, i.e., protein synthesis is required post-insult. These three apoptotic mechanisms each access one of two "points-of-no-return" located on the mitochondrial membrane, which activate different, but not mutually exclusive, final pathways of apoptosis. This review discusses the latest findings on these apoptotic mechanisms and their implications in phototherapies.