UVB-induced apoptosis

UV-induced apoptosis UV-induced apoptosis is an adequate (physiological) reaction of a cell damaged by UV radiation (UVR) in a sufficiently large (lethal) dose and it prevents the disordered destruction of UV damaged cells by help necrosis. Cell elimination by apoptosis occurs when UV-induced cell damage which cannot be repaired by the intracellular repair system exceeds at it certain limit (lethal damage). Through apoptosis, the cells are self-disassembled into compartments with their subsequent utilization (mainly by neighboring cells). The first time sign of the beginning of the apoptosis system is working in a UV damaged cell is the activation of restriction enzymes,  which divide cell DNA into fragments convenient for utilization. But too large a dose of UVR can lead to breakdown (inactivation) of the energy-dependent mechanism of apoptosis (super lethal damage). In this case, cell destruction occurs randomly, not orderly, and during a significantly longer (compared with apoptosis) time interval. UV-irradiated cells do not change their appearance for a long time [1, 6], as a result of which the researchers may make the erroneous conclusion that “revealed an unexpected response to a dose at which a higher dose of UV increased the viability of keratinocytes” [2]. The fact that UV-induced apoptosis at high doses of UVR begins to be replaced by necrosis was established in 2000 [3]. For keratinocytes, the proportion of cells that have elimination by help apoptosis, with an increase in UVR dose can reach to achieve 45%, but with a further increase in the dose of UVR (due to the shutdown of the mechanism of apoptosis), destruction of damaged cells by help necrosis and the part of cells that eliminated by apoptosis begins to decrease (non-monotonous dose dependence of UV-induced apoptosis) [4, 11]. In the dose range of UVR from “lethal” to “super-lethal”, “pro-inflammatory” apoptosis can be manifested, which was experimentally discovered in 2003 [5]. This may be the result of partial damage to the apoptosis mechanism by UV radiation [1]. If at moderate doses “pure” apoptosis does not cause an inflammatory reaction, then at sufficiently large (but lower than superlethal) doses, an inflammatory reaction arises due to pro-inflammatory apoptosis, which leads to the appearance of “fast” erythema for UV irradiated skin keratinocytes. Kinetic of “fast” erythema is much faster by the time of development of UV erythema caused by necrosis of UV damaged keratinocytes [6]. The most erythemogenic is UVB (UVB, 280 - 320 nanometers) the spectral range of UVR, since radiation in this range is less absorbed by the outer layers of the skin, which allows UVB radiation, in contrast to UVC (UVC, 200 - 280 nm), to reach more deep layers skin and act on keratinocytes of the deep-lying basal layer of the epidermis of the skin. The ability to induce apoptosis for UVB and UVC radiation is due to the fact that the DNA of the nucleus [7] and / or mitochondria [8] of the cell absorbs UVR well in the UVC and UVB spectral range. Keratinocytes of the skin (regardless of UVR exposure) are in a state of programmed apoptosis, during which the keratinocytes of the basal layer are removed from it and during the transition through all layers of the epidermis within 28 days turn into flakes of the outer stratum corneum, which are subsequently desquamated. It is clear that the keratinocyte response to UV exposure will depend on what phase of programmed apoptosis (at what distance from the basal layer) the keratinocyte experienced UV exposure, and this is the main reason for the difference of the UV effect for UVC and UVB on the skin. There are also differences in the initiation of mitochondrial (internal) and caspase-dependent (external) apoptosis for the UVC and UVB spectral ranges [9]. Sunburn cells (SBS) are the keratinocytes in the process of UV-induced apoptosis (both “pure” and pro-inflammatory). The appearance of SBC may be not associated with an inflammatory reaction, but the role of UV-induced apoptosis of skin keratinocytes in the development of UV erythema (hyperemia, redness) of the skin has been established, which allowed the development of a patent-protected METHOD FOR QUANTITATIVE ASSESSMENT OF APOPTOSIS SYSTEM [10], in which “the brightest lamp of skin display "(photoerythema) is used (as an indicator of the manifestation of strictly dosed sterile inflammation) to diagnose the state of the body systems involved in the elimination of UV-induced damage.  Such systems (except apoptosis) include the immune system, the intracellular repair system, the microcirculation system and not only.

UVB-induced apoptosis pathway
The sequence of events that leads to apoptosis is multifaceted and complex. Despite the simple concept of apoptosis, the sequence of events that leads to it and other conditions that attempt to counter act it can be very cumbersome. Since apoptosis is a last resort alternative, it takes the initiation of multiple other genes (ING2, p53, or Ras subfamily) expressed before the cell is finally programmed for death. In addition, genes like Survivin can attempt to suppress apoptosis.