Effect of ultraviolet A on ornithine decarboxylase and metallothionein gene expression in mouse skin.
BACKGROUND
Ultraviolet A (UVA) is known to induce the expression of many stress responsive genes due to the generation of reactive oxygen species (ROS). However, UVA's role in inducing metallothionein (MT) gene expression has not been studied. Furthermore, our group demonstrated that UVA enhanced 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated induction of ornithine decarboxylase (ODC) activity in mouse skin (1).


METHODS
We examined the interaction of UVA, TPA and antioxidants on the induction of MT and ODC mRNA in mouse skin. Female CD-1 mice were exposed to UVA (19 J/cm2) and total RNA was isolated from the skin. Northern blot analysis for MT and ODC mRNAs was performed. ODC activity in mouse epidermis was also determined in some experiments.


RESULTS
UVA induced MT mRNA in mouse skin; however, it did not increase ODC mRNA. 1,4-Diazabicylo-[2,2,2]-octane (DABCO), a singlet oxygen scavenger, reduced UVA-mediated induction of MT mRNA by 40%. The data suggest that ROS produced by UVA exposure may contribute to its ability to induce MT mRNA. UVA slightly enhanced TPA-mediated ODC mRNA induction, while it enhanced ODC enzyme activity 70%. UVA additively intensified TPA-mediated MT mRNA induction. alpha-Tocopherol pretreatment inhibited the induction of ODC enzyme activity by TPA treatment combined with UVA exposure (TPA + UVA); however, alpha-tocopherol had less of an inhibitory effect on ODC mRNA induction by TPA + UVA. Curcumin, a plant pigment, dramatically inhibited both TPA- and TPA + UVA-induced expression of ODC and MT genes.


CONCLUSIONS
These results demonstrate that UVA can induce MT gene expression and enhance TPA-induced ODC and MT gene expression. The data further suggest that these effects are partially mediated by ROS.
Oguro
T
T
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. oguro@pharm.showa-u.ac.jp
Yoshida
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015152:Blotting, Northern; D003474:Curcumin / Q000494:pharmacology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects*; D008668:Metallothionein / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011837:Radiation-Protective Agents / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D010879:Piperazines; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D014810:Vitamin E; D008668:Metallothionein; D009955:Ornithine Decarboxylase; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; C007306:triethylenediamine