Neuroprotectin D1 induces dephosphorylation of BCL-XL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival
ABSTRACT Retinal pigment epithelial (RPE) cell integrity is critical for the survival of photoreceptor cells. Bcl-x(L) is a major anti-apoptotic Bcl-2 protein required for RPE cell survival, and phosphorylation of Bcl-x(L) at residue Ser-62 renders this protein pro-apoptotic. In this study, we identify serine/threonine protein phosphatase 2A (PP2A) as a key regulator of Bcl-x(L) phosphorylation at residue Ser-62 in ARPE-19 cells, a spontaneously arising RPE cell line in which Bcl-x(L) is highly expressed. We found that either PP2A inhibitor okadaic acid or depletion of catalytic subunit alpha of PP2A (PP2A/Calpha) by small interfering RNA enhanced Bcl-x(L) phosphorylation when activated with hydrogen peroxide and tumor necrosis factor alpha-induced oxidative stress. Disruption of PP2A/Calpha exacerbated oxidative stress-induced apoptosis. PP2A/Calpha colocalized and interacted with S62Bcl-x(L) in cells stressed with H(2)O(2)/tumor necrosis factor alpha. By contrast, the omega-3 fatty acid docosahexaenoic acid derivative, neuroprotectin D1 (NPD1), a potent activator of survival signaling, down-regulated oxidative stress-induced phosphorylation of Bcl-x(L) by increasing protein phosphatase activity. NPD1 also attenuated the oxidative stress-induced apoptosis by knockdown of PP2A/Calpha and increased the association of PP2A/Calpha with S62Bcl-x(L) as well as total Bcl-x(L). NPD1 also enhanced the heterodimerization of Bcl-x(L) with its counterpart, pro-apoptotic protein Bax. Thus, NPD1 modulates the activation of this Bcl-2 family protein by dephosphorylating in a PP2A-dependent manner, suggesting a coordinated, NPD1-mediated regulation of cell survival in response to oxidative stress.
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ABSTRACT: Differences in electrical characteristics of barbed plate-to-plate and wire-plate precipitators are presented in terms of measured current-voltage curves and spatial distributions of current at the collection plate. Data are obtained in a 61.0 cm by 61.0 cm by 15.2 cm laboratory precipitator operating at Reynolds and electrohydrodynamic numbers typical of industrial precipitators. Results show that a barbed plate-to-plate precipitator produces more uniform distributions of current along the collector plates than exist in a conventional wire-plate precipitatorIndustry Applications Society Annual Meeting, 1993., Conference Record of the 1993 IEEE; 11/1993
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ABSTRACT: A new genus of specialized pro-resolving mediators (SPM) which include several families of distinct local mediators (lipoxins, resolvins, protectins, and maresins) are actively involved in the clearance and regulation of inflammatory exudates to permit restoration of tissue homeostasis. Classic lipid mediators that are temporally regulated are formed from arachidonic acid, and novel local mediators were uncovered that are biosynthesized from ω-3 poly-unsaturated fatty acids, such as eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid. The biosynthetic pathways for resolvins are constituted by fatty acid lipoxygenases and cyclooxygenase-2 via transcellular interactions established by innate immune effector cells which migrate from the vasculature to inflamed tissue sites. SPM provide local control over the execution of an inflammatory response towards resolution, and include recently recognized actions of SPM such as tissue protection and host defense. The structural families of the SPM do not resemble classic eicosanoids (PG or LT) and are novel structures that function uniquely via pro-resolving cellular and molecular targets. The extravasation of inflammatory cells expressing SPM biosynthetic routes are matched by the temporal provision of essential fatty acids from circulation needed as substrate for the formation of SPM. The present review provides an update and overview of the biosynthetic pathways and actions of SPM, and examines resolution as an integrated component of the inflammatory response and its return to homeostasis via biochemically active resolution mechanisms.Biochimica et Biophysica Acta 12/2010; 1801(12):1260-73. DOI:10.1016/j.bbalip.2010.08.002 · 4.66 Impact Factor