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      Erratum: Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2

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          Abstract

          Scientific Reports 7:1110; doi:10.1038/s41598-017-01016-8; Article published online 24 April 2017 The original version of this Article contained errors. In the Abstract, “The use of SC79, an Akt1/2 inhibitor” now reads: “The use of SC79, an Akt1/2 activator” In the Introduction, “wildlife and animal exposure including fetal growth” now reads: “wildlife and animal exposure including reduced fetal growth” In addition, “inducing Sertoli cell injury and Leydig cell steroidogenic function” now reads: “inducing Sertoli cell injury and disrupting Leydig cell steroidogenic function” Finally, “This mechanistic study thus provides additional insight on the molecular mechanism by which PFOS mediates reproductive” now reads: “This mechanistic study thus provides additional insight on the molecular mechanism by which PFOS causes reproductive” The original version of this Article omitted Xiang Xiao and Wing-yee Lui as corresponding authors. Correspondence and request for materials should also be addressed to X.X. (xxiao@zjams.com) or W.Y.L. (wylui@hku.hk) In the Results section, under the sub-heading ‘PFOS perturbs Sertoli cell TJ-barrier function through changes in the spatial expression of actin binding and regulatory proteins’, “Palladin also no longer stretched across the Sertoli cell cytosol to organize actin filaments into bundles, instead, paladin retracted from cell cytosol and found closer to the cell nuclei (Fig. 2).” now reads: “Palladin also no longer stretched across the Sertoli cell cytosol to organize actin filaments into bundles as seen in controls, instead, palladin retracted from cell cytosol and found closer to the cell nuclei following PFOS treatment (Fig. 2)” The Results section contains an error in a sub-heading, where: “Rescue of PFOS-induced Sertoli cell TJ-barrier disruption by SC79, an activator of Akt through changes in the re-distribution of BTB-associated proteins.” now reads: “Rescue of PFOS-induced Sertoli cell TJ-barrier disruption by SC79, an activator of Akts through changes in the re-distribution of BTB-associated proteins.” There were also errors in the Figure legends. In Figure 2 legend, “Instead, palladin was retraced from the cell peripheries but concentrated to cell nuclei after PFOS treatment.” now reads: “Instead, palladin was retracted from the cell peripheries but concentrated to cell nuclei after PFOS treatment.” In Figure 3(c) legend “(C) Sertoli cells cultured at 0.04 × 106 cells/cm2 for 3 days were pre-treated with 2 μg/ml SC79 for 30 min, and then cells were rinsed and treated with 20 μM PFOS for 24 hr. Thereafter, cells were then fixed and examined by immunofluorescence microscopy. SC79 treatment was found to block PFOSinduced mis-localization of TJ proteins CAR and ZO-1, as well as basal ES proteins N-cadherin and β-catenin, apparently through enhanced endocytosis. BTB-associated proteins at the Sertoli cell-cell interface in control and treated cells were annotated by corresponding white and yellow brackets, respectively” now reads: “(C) Sertoli cells cultured at 0.04 × 106 cells/cm2 for 3 days were pre-treated with 2 μg/ml SC79 for 30 min, and then cells were rinsed and treated with 20 μM PFOS for 24 hr. Thereafter, cells were then fixed and examined by immunofluorescence microscopy. SC79 treatment was found to block PFOS-induced mis-localization of TJ proteins CAR and ZO-1, as well as basal ES proteins N-cadherin and β-catenin. BTB-associated proteins at the Sertoli cell-cell interface in control and PFOS-treated cells were annotated by corresponding white and yellow brackets, respectively” In Figure 4 legend “yellow rectangles in FOS-treated cells” now reads: “yellow rectangles in PFOS-treated cells” In Figure 5 legend, Figure 1A now reads Figure 1B In Figure 6 legend, “Thereafter, cells were fixed with ice-cold methanol and visualized byimmunofluorescence microscopy.” now reads: “Thereafter, cells were fixed with ice-cold methanol and visualized by immunofluorescence microscopy using corresponding antibodies (Table 1)” In addition, the Acknowledgments section now reads: We wish to thank Dr. Ben Margolis and Dr. Shuling Fan who kindly provided us with some anti-CRB3 antibody to validate some experiments in this report. This work was supported by grants from the National Institutes of Health (R01 HD056034 to C.Y.C.; U54 HD029990 Project 5 to C.Y.C.); National Natural Science Foundation of China (NSFC) (31371176 to X.X.), Qianjiang Talents Program (QJD1502029 to X.X.), Zhejiang Province Funding (Science Technology Department, 2016F10010 to X.X.); Hong Kong Research Grants Council (RGC) General Research Fund (GRF) (774213 and 17100816 to W.Y.L.; 771513 to W.M.L.), NSFC/RGC Joint Research Scheme (N_HKU 717/12 to W.M.L.), and University of Hong Kong CRCG Seed Funding (to W.M.L.) The Author Contributions statement now reads: C.Y.C., Y.G. and H.C. designed research; Y.G., H.C. and C.Y.C. performed research; X.X., W.Y.L., W.M.L., D.D.M. and C.Y.C. contributed new reagents/analytic tools; Y.G., H.C. and C.Y.C. analyzed data; Y.G. and C.Y.C. wrote the paper; Y.G., H.C. and C.Y.C. prepared all figures. All authors reviewed the manuscript. There were also errors in References 43 and 76, which now read: 43. Li, N., Mruk, D. D., Lee, W. M., Wong, C. K. C. & Cheng, C. Y. Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis? Semin Cell Dev Biol 59, 141–156, doi:10.1016/j.semcdb.2016.01.003 (2016). 76. Gong, Y. et al. SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling. Oncotarget 7, 60123–60132, doi:10.18632/oncotarget.11164 (2016). These errors have now been corrected in the HTML and PDF versions of this Article.

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          SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

          Excessive Ultra-violet (UV) radiation causes oxidative damages and apoptosis in retinal pigment epithelium (RPE) cells. Here we tested the potential activity of SC79, a novel small molecule activator of Akt, against the process. We showed that SC79 activated Akt in primary and established (ARPE-19 line) RPE cells. It protected RPE cells from UV damages possibly via inhibiting cell apoptosis. Akt inhibition, via an Akt specific inhibitor (MK-2206) or Akt1 shRNA silence, almost abolished SC79-induced RPE cytoprotection. Further studies showed that SC79 activated Akt-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited UV-induced oxidative stress in RPE cells. Reversely, Nrf2 shRNA knockdown or S40T mutation attenuated SC79-induced anti-UV activity. For the in vivo studies, we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages. Based on these results, we suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis.
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            Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?

            Sertoli cells isolated from rodents or humans and cultured in vitro are known to establish a functional tight junction (TJ)-permeability barrier that mimics the blood-testis barrier (BTB) in vivo. This model has been widely used by investigators to study the biology of the TJ and the BTB. Studies have shown that environmental toxicants (e.g., perfluorooctanesulfonate (PFOS), bisphenol A (BPA) and cadmium) that exert their disruptive effects to induce Sertoli cell injury using this in vitro model are reproducible in studies in vivo. Thus, this in vitro system provides a convenient approach to probe the molecular mechanism(s) underlying toxicant-induced testis injury but also to provide new insights in understanding spermatogenesis, such as the biology of cell adhesion, spermatid transport, and others. Herein, we provide a brief and critical review based on studies using this in vitro model of Sertoli cell cultures using primary cells isolated from rodent testes versus humans to monitor environmental toxicant-mediated Sertoli cell injury, and this information is relevant to the molecular mechanisms that regulate spermatogenesis. In short, recent findings have shown that environmental toxicants exert their effects on Sertoli cells to induce testis injury through their action on Sertoli cell actin- and/or microtubule-based cytoskeleton. These effects are mediated via their disruptive effects on actin- and/or microtubule-binding proteins. Sertoli cells also utilize differential spatiotemporal expression of these actin binding proteins to confer plasticity to the BTB to regulate germ cell transport across the BTB.
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              Author and article information

              Contributors
              xxiao@zjams.com
              wylui@hku.hk
              Y-Cheng@popcbr.rockefeller.edu
              Journal
              Sci Rep
              Sci Rep
              Scientific Reports
              Nature Publishing Group UK (London )
              2045-2322
              26 July 2017
              26 July 2017
              2017
              : 7
              : 6950
              Affiliations
              [1 ]ISNI 0000 0004 0441 8543, GRID grid.250540.6, The Mary M. Wohlford Laboratory for Male Contraceptive Research, , Center for Biomedical Research, Population Council, ; 1230 York Ave, New York, New York, 10065 USA
              [2 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Department of Reproductive Physiology, , Zhejiang Academy of Medical Sciences, ; Hangzhou, 310013 China
              [3 ]School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong China
              Author information
              http://orcid.org/0000-0003-3117-3791
              Article
              4863
              10.1038/s41598-017-04863-7
              5529478
              28747671
              969f9815-e44e-4b19-be16-935101e8e27d
              © The Author(s) 2017

              Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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