Selective Transcription Factor Induction in Retinal Pigment Epithelial Cells during Photoreceptor Phagocytosis

Ershov, A. V.; Lukiw, Walter J.; Bazán, Nicolás G.

doi:10.1074/jbc.271.45.28458

Cited by 28 publications

(24 citation statements)

References 38 publications

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“…The molecular mechanism of RPE phagocytosis remains largely unclear, but appears to be OS specific, at least at the level of the initial events of recognition, binding, and internalization. Numerous studies in RCS rats have suggested that the RPE utilizes distinct mechanisms for uptake of OS and latex microspheres [7][8][9][10]. The c-mer receptor tyrosine RPE cell culture Primary cultures of human RPE cells (hRPE) were a gift from Dr. J. Burke (Medical College of Wisconsin, Wis.), and were obtained as confluent cell monolayers at early passages ranging from 3 to 8.…”

mentioning

confidence: 99%

Accumulation of oxidized lipid-protein complexes alters phagosome maturation in retinal pigment epithelium

Hoppe

O’Neil

Hoff

et al. 2004

CMLS, Cell. Mol. Life Sci.

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Lipid peroxidation has been implicated in many age-associated disorders including macular degeneration of the retina. We sought to elucidate the mechanism by which accumulation of oxidized LDL (oxLDL) reduces the ability of retinal pigment epithelium (RPE) to process photoreceptor outer segments (OS) as a model of peroxidation-induced disruption of phagocytosis. OxLDL did not reduce the lysosomal hydrolytic capacity of the RPE, but efficiently inhibited processing of various internalized proteins. OxLDL caused a delay in the acquisition of late lysosomal markers by newly formed phagosomes. At the same time, an excessive accumulation of markers of early phagosomal compartments was also observed. The activity of phosphatidylinositol 3-kinase (PI3K) was reduced in phagosomes of the RPE treated with oxLDL. These results suggest that accumulation of oxidized lipid-protein complexes in the RPE impedes phagosome maturation by blocking PI3K recruitment to the phagosomal membrane, leading to delayed processing of internalized OS.

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mentioning

confidence: 99%

Accumulation of oxidized lipid-protein complexes alters phagosome maturation in retinal pigment epithelium

Hoppe

O’Neil

Hoff

et al. 2004

CMLS, Cell. Mol. Life Sci.

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“…Ershov and co-workers [12] have shown that the expression of the transcription factors AP-1 and AP-2 is increased in RPE cells after ROS phagocytosis. These transcription factors may then bind the tyrosinase gene promoter at their corresponding binding sites [13] and thereby upregulate transcription of tyrosinase.…”

Section: Discussionmentioning

confidence: 98%

Tyrosinase biosynthesis and trafficking in adult human retinal pigment epithelial cells

Julien

Kociok²,

Kreppel

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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“…The increase in NPD1 was almost six times higher than that of RPE cells exposed to microspheres. Outer segment phagocytosis also triggered early response gene induction [21], as well as COX-2 [22] and PPARγ [23] expression.…”

Section: Photoreceptor Outer Segment Phagocytosis Selectively Attenuamentioning

confidence: 97%

Docosanoids are multifunctional regulators of neural cell integrity and fate: Significance in aging and disease

Mukherjee

Chawla

Loayza

et al. 2007

Prostaglandins, Leukotrienes and Essential Fatty Acids

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The identification of neuroprotectin D1 (NPD1), a biosynthetic product of docosahexaenoic acid (DHA), in brain and retina as well as the characterization of its bioactivity, is generating a renewed interest in the functional role and pathophysiological significance of omega-3 fatty acids in the central nervous system.Neurotrophins, particularly pigment epithelium-derived factor (PEDF), induce NPD1 synthesis and its polarized apical secretion, implying paracrine and autocrine bioactivity of this lipid mediator. Also, DHA and PEDF synergistically activate NPD1 synthesis and antiapoptotic protein expression and decreased proapoptotic Bcl-2 protein expression and caspase 3 activation during oxidative stress.In experimental stroke, endogenous NPD1 synthesis was found to be upregulated, and the infusion of the lipid mediator into the brain under these conditions revealed neuroprotective bioactivity of NPD1.The hippocampal CA1 region from Alzheimer's disease (AD) patients (rapidly sampled) shows a major reduction in NPD1.The interplay of DHA-derived neuroprotective signaling aims to counteract proinflammatory, celldamaging events triggered by multiple, converging cytokine and amyloid peptide factors, as in the case of AD. Generation of NPD1 from DHA thereby appears to redirect cellular fate toward successful preservation of retinal pigment epithelial (RPE)-photoreceptor cell integrity and brain cell aging. The Bcl-2 pro-and antiapoptotic proteins, neurotrophins, and NPD1, lie along a cell fateregulatory pathway whose component members are highly interactive, and have potential to function cooperatively in cell survival. Agents that stimulate NPD1 biosynthesis, NPD1 analogs, or dietary regimens may be useful as new preventive/therapeutic strategies for neurodegenerative diseases.

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Selective Transcription Factor Induction in Retinal Pigment Epithelial Cells during Photoreceptor Phagocytosis

Abstract: Expression of early response genes during rod outer segment phagocytosis by normal Long Evans and Royal College of Surgeons-rdy

Cited by 28 publications

References 38 publications

Accumulation of oxidized lipid-protein complexes alters phagosome maturation in retinal pigment epithelium

Accumulation of oxidized lipid-protein complexes alters phagosome maturation in retinal pigment epithelium

Tyrosinase biosynthesis and trafficking in adult human retinal pigment epithelial cells

Docosanoids are multifunctional regulators of neural cell integrity and fate: Significance in aging and disease

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