Urocanic acid (UCA) is present at millimolar concentrations in mammalian epidermis and undergoes photoisomerization from the naturally occurring trans-isomer to the cis-isomer on exposure to ultraviolet radiation (UVR). Cis-UCA causes downregulation of various immune responses in mouse and human experimental models and has been proposed as both a chromophore and a mediator of UV-induced immune suppression. In this study, the wavelength dependence from 260-340 nm for trans to cis-UCA photoisomerization in human skin was analyzed in five healthy volunteers. The resulting action spectrum demonstrated maximal cis-UCA production in the UVB spectral region of 280-310 nm. This spectral peak is red-shifted to longer wavelengths compared with the erythemal action spectrum. The cis-UCA action spectrum can be used to predict the ability of sunscreens to protect against UVR-induced cis-UCA formation and may assist in explaining discrepancies between sunscreens' abilities to protect against erythema and photoimmunosuppression.

Transglutaminase 2 (TG2) is a multifunctional protein that can contribute to cell death and cell survival processes in a variety of disease contexts. Within the brain, TG2 has been shown to promote cell death in ischemic injury when expressed in astrocytes (Colak and Johnson, 2012). However, the specific functions and characteristics of astrocytic TG2 that mediate this effect are largely unknown. Therefore, the goal of this study was to investigate the role of astrocytic TG2 in mediating cellular viability processes in the context of ischemic injury, with a specific focus on its contributions to intracellular signaling cascades. We show that, in response to oxygen/glucose deprivation (OGD), acute lentiviral-mediated knockdown of TG2, as well as inhibition with an irreversible TG2 inhibitor, enhances cell survival. We also show that TG2 depletion increases nuclear factor-κB (NF-κB) signaling, whereas inhibition reduces NF-κB activity. Despite its clear contribution to NF-κB signaling, however, TG2 modulation of NF-κB signaling is not likely to be a major contributor to its ability to mediate astrocytic viability in this context. Overall, the results of this study provide insight into the role of TG2 in astrocytes and suggest possible avenues for future study of the relationship between astrocytic TG2 and ischemic injury.

No abstract