Sulforaphane promotes ER stress, autophagy and cell death: implications for cataract surgery

Liu, Hanruo, Smith, Andrew J. O., Ball, Simon S. R., Bao, Yongping, Bowater, Richard P., Wang, Ningli and Wormstone, I. Michael (2017) Sulforaphane promotes ER stress, autophagy and cell death: implications for cataract surgery. Journal of Molecular Medicine, 95 (5). 553–564. ISSN 0946-2716

[img] PDF (Accepted manuscript) - Submitted Version
Restricted to Repository staff only until 31 December 2099.

Download (796kB) | Request a copy
    [img]
    Preview
    PDF (Liu et all- JMolMed 2017) - Published Version
    Available under License Creative Commons Attribution.

    Download (1931kB) | Preview

      Abstract

      Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyanate, sulforaphane (SFN) is reported to exert cytoprotective and cytotoxic actions and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10µM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of ER stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased LC3-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling and inhibition of ERK activation using U0126 prevented SFN induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO.

      Item Type: Article
      Additional Information: © The Author(s) 2017 Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
      Uncontrolled Keywords: sulforaphane, er stress,lens,posterior capsule opacificatio,autophagy flux
      Faculty \ School: Faculty of Science > School of Biological Sciences
      Faculty of Medicine and Health Sciences > Norwich Medical School
      Related URLs:
      Depositing User: Pure Connector
      Date Deposited: 08 Dec 2016 00:07
      Last Modified: 14 Dec 2018 01:00
      URI: https://ueaeprints.uea.ac.uk/id/eprint/61648
      DOI: 10.1007/s00109-016-1502-4

      Actions (login required)

      View Item