Abstract
Reactive Oxygen Species (ROS) are reactive molecules required for the maintenance of physiological functions. Oxidative stress arises when ROS production exceeds the cellular ability to eliminate such molecules. In this study, we showed that oxidative stress induces post-translational modification of the inner nuclear membrane protein emerin. In particular, emerin is phosphorylated at the early stages of the oxidative stress response, while protein phosphorylation is abolished upon recovery from stress. A finely tuned balance between emerin phosphorylation and O-GlcNAcylation seems to govern this dynamic and modulates emerin–BAF interaction and BAF nucleoplasmic localization during the oxidative stress response. Interestingly, emerin post-translational modifications, similar to those observed during the stress response, are detected in cells bearing LMNA gene mutations and are characterized by a free radical generating environment. On the other hand, under oxidative stress conditions, a delay in DNA damage repair and cell cycle progression is found in cells from Emery–Dreifuss Muscular Dystrophy type 1, which do not express emerin. These results suggest a role of the emerin–BAF protein platform in the DNA damage response aimed at counteracting the detrimental effects of elevated levels of ROS.
Highlights
Oxidative stress is defined as an imbalance between the production of reactive free radicals and the efficacy of antioxidant defenses
Immunological staining of phopho-ERK1/2 confirmed the efficacy of O.A. and OSMI-1 in single or combined treatments in the presence of H2O2 (Figure 2d). These results strongly suggest that the molecular weight shift in emerin during the initial step of the oxidative stress response is due to protein phosphorylation which is favored by a decrease in O-GlcNAcylation (Berk)
To further investigate the increase in emerin phosphorylation increase during the oxidative stress response, HeLa cells were treated with H2 O2 in combination with Okadaic Acid (O.A.), a specific inhibitor of serine/threonine protein phosphatases (Figure 2b)
Summary
Oxidative stress is defined as an imbalance between the production of reactive free radicals and the efficacy of antioxidant defenses. Production of free radicals is a physiological event taking place at the cellular level. These free radicals are important mediators of responses leading to cellular migration, differentiation, and proliferation; when cells become unable to control the amount of free radicals, oxidative stress arises [1]. In this regard, to avoid excessive Reactive Oxygen Species (ROS) accumulation, cells have developed several antioxidant systems, including enzymatic and non-enzymatic mechanisms, that limit protein, lipid, and DNA oxidation [2]. A similar metabolic status occurs as a result of genetic mutations affecting some nuclear envelope proteins [3,4,5,6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
