Hajime Nakano

UVA-340 as Energy Source, Mimicking Natural Sunlight, Activates the Transcription Factor AP-1 in Cultured Fibroblasts: Evidence for Involvement of Protein Kinase-C¶

Abstract Ultraviolet radiation (UVR) is known to affect a variety of cellular functions, including gene expression. A number of signaling pathways have been suggested to mediate these effects, including the participation of activator protein-1 (AP-1), activator protein-2 (AP-2) and nuclear factor-κB (NF-κB). The divergent results from previous studies could be explained, at least in part, by the source of UVR with different spectral characteristics as well as the type of cells employed as targets. In this study we have utilized UVA-340 as an energy source with output which closely matches the spectrum of natural sunlight over the range of 295–350 nm for irradiation of cultured fibroblasts. Combination of electrophoretic mobility shift assays and Northern analyses revealed activation of AP-1 but not NF-κB or AP-2. Inhibition studies further suggested the participation of protein kinase-C, but not protein kinase-A, and that an inhibitor of mitogen-activated protein kinase (MEK-1/2) did not alter the AP-1 activation. Free radical quenchers, sodium azide and N-acetylcysteine, did not affect the AP-1 binding activity. Finally, UVA-340 was shown to enhance transcriptional expression of the type-VII collagen gene (COL7A1), which is endogenously expressed in dermal fibroblast in an AP-1 dependent manner. Introduction of a mutation into the AP-1 site of the COL7A1 promoter abolished this activation. Thus, our results obtained by utilizing a novel energy source, UVA-340, mimicking natural sunlight at UVB and lower UVA range indicate a role for AP-1 in mediating the enhanced gene expression by UVR. Collectively, these results suggest that AP-1 is an important mediator of UVR action in fibroblasts.

ZNT4 gene is not responsible for acrodermatitis enteropathica in Japanese families

We read with great interest a recent paper by Küry et al. (2001), describing the absence of mutations in the human ZNT4 gene (also known as SLC30A4) in 10 patients with acrodermatitis enteropathica (AE). AE is a rare autosomal recessive disease manifesting with acral dermatitis and low serum zinc level. ZNT4 encodes one of the zinc-transport proteins, Znt4, and is expressed in mammary epithelia and brain (Huang and Gitschier 1997). A previous study has revealed that the lethal milk mouse, a putative animal model for AE, is caused by a nonsense mutation (R297X) in mouse Znt4 (Huang and Gitschier 1997), suggesting a possible relationship between AE and human ZNT4, which has been mapped to chromosomal region 15q15 (Küry et al. 2001). In search of the candidate gene for AE, we have characterized the exon/intron organization of the human ZNT4 gene and screened ZNT4 for mutations in two Japanese AE families.