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Development of refractoriness of ho-1 induction to a second treatment with uva radiation and the involvement of nrf2 in human skin fibroblasts


Reference:

Zhong, J. L., Raval, C. M., Nisar, M. F., Bian, C., Zhang, J., Yang, L. and Tyrrell, R. M., 2014. Development of refractoriness of ho-1 induction to a second treatment with uva radiation and the involvement of nrf2 in human skin fibroblasts. Photochemistry and Photobiology, 90 (6), pp. 1340-1348.

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      Official URL:

      http://dx.doi.org/10.1111/php.12343

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      Abstract

      UVA treatment of cultured human skin fibroblasts (FEK4) has been shown previously to reduce transcriptional activation of heme oxygenase 1 (HO-1) following a second dose of UVA radiation, a phenomenon known as refractoriness. This study demonstrates that the levels of HO-1 protein are also reduced after a second dose of UVA radiation as are Nrf2 levels, and there is less accumulation of Nrf2 in the nucleus where as Bach1 does accumulate in the nucleus. Cell viability is further reduced and cell membrane damage increased as compared with a single UVA treatment when an initial UVA treatment was followed by a second dose. Knockdown of Nrf2 by siRNA (siNrf2) targeting caused additional refractoriness of HO-1 protein induction to a second UVA or heme treatment and this treatment also further enhanced cell damage by a second dose of UVA radiation. However, transfection with Nrf2 caused less refractoriness of HO-1 to a second dose of UVA and reduced cell damage by a second dose of UVA radiation. These findings are consistent with the proposal that Nrf2 is involved in HO-1 refractoriness and could serve as a cytoprotective factor against cell damage caused by repeated exposure to moderate doses of UVA radiation. We propose that protection by the Nrf2-HO-1 pathway protection may have clinical relevance since human skin is exposed repeatedly to UVA radiation.

      Details

      Item Type Articles
      CreatorsZhong, J. L., Raval, C. M., Nisar, M. F., Bian, C., Zhang, J., Yang, L. and Tyrrell, R. M.
      DOI10.1111/php.12343
      Related URLs
      URLURL Type
      http://www.scopus.com/inward/record.url?scp=84915751101&partnerID=8YFLogxKUNSPECIFIED
      DepartmentsFaculty of Science > Pharmacy & Pharmacology
      Publisher StatementFigs_for_Refr.ctoriness_paper.pdf: This is the peer reviewed version of the following article: Zhong, JL, Raval, CM, Nisar, MF, Bian, C, Zhang, J, Yang, L & Tyrrell, RM 2014, 'Development of refractoriness of ho-1 induction to a second treatment with uva radiation and the involvement of nrf2 in human skin fibroblasts' Photochemistry and Photobiology, vol 90, no. 6, pp. 1340-1348., which has been published in final form at http://dx.doi.org/10.1111/php.12343. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving;development_of_refractoriness_of_ho_1.pdf: This is the peer reviewed version of the following article: Zhong, JL, Raval, CM, Nisar, MF, Bian, C, Zhang, J, Yang, L & Tyrrell, RM 2014, 'Development of refractoriness of ho-1 induction to a second treatment with uva radiation and the involvement of nrf2 in human skin fibroblasts' Photochemistry and Photobiology, vol 90, no. 6, pp. 1340-1348., which has been published in final form at http://dx.doi.org/10.1111/php.12343. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving
      RefereedYes
      StatusPublished
      ID Code43341

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