Biphasic response of the metallothionein promoter to ultraviolet radiation in human melanoma cells

Hansen, C., Ablett, E., Green, A., Sturm, R. A., Dunn, I. S., Fairlie, D. P., West, M. L. and Parsons, P. G. (1997) Biphasic response of the metallothionein promoter to ultraviolet radiation in human melanoma cells. Photochemistry and Photobiology, 65 3: 550-555. doi:10.1111/j.1751-1097.1997.tb08603.x

Author Hansen, C.
Ablett, E.
Green, A.
Sturm, R. A.
Dunn, I. S.
Fairlie, D. P.
West, M. L.
Parsons, P. G.
Title Biphasic response of the metallothionein promoter to ultraviolet radiation in human melanoma cells
Journal name Photochemistry and Photobiology   Check publisher's open access policy
ISSN 0031-8655
Publication date 1997-03
Sub-type Article (original research)
DOI 10.1111/j.1751-1097.1997.tb08603.x
Volume 65
Issue 3
Start page 550
End page 555
Total pages 6
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell
Language eng
Formatted abstract
Because metallothionein (MT) is elevated and may be protective in UV-irradiated skin, we have studied the effects of UV and other agents on MT transcription using the sheep MT 1A promoter, linked to the β-galactosidase gene and stably transfected into human cell lines. β-Galactosidase reporter activity was inducible by adding Zn 2+ ions to the medium (100 μM for 2-4 h). Two differentiating agents, butyric acid and azelaic bishydroxamic acid (ABHA), significantly increased the response to Zn 2+ in a melanoma cell line (MM96L-gal). UVB (280315 nm) had two distinct, time-dependent effects. During the first 4 h after irradiation, high doses of UVB inhibited induction by Zn 2+, an effect that was made more acute by simultaneous exposure to the differentiating agents. These changes in reporter activity were not due to alterations in Zn 2+ transport into the cell. The UVB-depressed MT response subsequently recovered and by 24 h was double the control, yet remained sensitive to ABHA. Reporter activity in transfected HeLa cells differed from that in MM96L, being depressed 4 and 24 h after UVB and insensitive to ABHA at both times. Galactosidase reporter activity driven by non-MT promoters was not affected by these treatments. Dependence of MT transcriptional activity on UV-related DNA damage could be inferred because equitoxic UVC (254 nm) affected the response to Zn 2+ in a similar fashion, whereas UVA, cisplatin and a methylating agent had no effect. The MT response was partly dependent on the PKC signal transduction pathway because it was inhibited by phorbol ester in HeLa, and by bisindolyl maleimide in HeLa and MM96L. The biphasic MT transcriptional response may model a signal transduction pathway that gives an early, depressed response to acute UV damage, with exacerbation by concurrent differentiation stimuli, but switches to a positive, cell-specific and potentially protective response at later times.
Keyword Protein-kinase-C
Human-skin Fibroblasts
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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