Binding of Pigment Epithelium-derived Factor (PEDF) to Retinoblastoma Cells and Cerebellar Granule Neurons

Alberdi, Elena; Aymerich, Marta; Becerra, S. Patricia

doi:10.1074/jbc.274.44.31605

Cited by 118 publications

(130 citation statements)

References 43 publications

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“…When PEDF is applied at concentrations similar to those used here to neuronal cells, it blocks rather than induces apoptosis (43)(44)(45). The PEDF survival signal to cerebellar granule cells appears to be mediated by an 80-kDa receptor (46). PEDF's action on endothelial cells is also likely to be receptormediated, but perhaps by way of a different receptor.…”

Section: Discussionmentioning

confidence: 98%

Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor

Stellmach

Crawford

Zhou

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

332

211

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Aberrant blood vessel growth in the retina that underlies the pathology of proliferative diabetic retinopathy and retinopathy of prematurity is the result of the ischemia-driven disruption of the normally antiangiogenic environment of the retina. In this study, we show that a potent inhibitor of angiogenesis found naturally in the normal eye, pigment epithelium-derived growth factor (PEDF), inhibits such aberrant blood vessel growth in a murine model of ischemia-induced retinopathy. Inhibition was proportional to dose and systemic delivery of recombinant protein at daily doses as low as 2.2 mg͞kg could prevent aberrant endothelial cells from crossing the inner limiting membrane. PEDF appeared to inhibit angiogenesis by causing apoptosis of activated endothelial cells, because it induced apoptosis in cultured endothelial cells and an 8-fold increase in apoptotic endothelial cells could be detected in situ when the ischemic retinas of PEDF-treated animals were compared with vehicle-treated controls. The ability of low doses of PEDF to curtail aberrant growth of ocular endothelial cells without overt harm to retinal morphology suggests that this natural protein may be beneficial in the treatment of a variety of retinal vasculopathies.

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Section: Discussionmentioning

confidence: 98%

Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor

Stellmach

Crawford

Zhou

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

332

211

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“…Because PEDF's neurotrophic͞neuroprotective activity has been attributed to a 44-aa region (24,25), we asked whether this region also possesses the permeability modulating activity. PEDF pep , which consists of amino acid residues 78-121 of human PEDF, was injected intravitreally in place of, and in equimolar amounts as, full-length PEDF.…”

Section: Resultsmentioning

confidence: 99%

“…4 a and b) and selected four candidate amino acid residues within PEDF for evaluation as the key moieties. Previous work (24,25) and our preliminary studies pointed to residues 78-121 of PEDF as the active site. From the crystal structure, the 44-aa region includes the complete secondary structural elements s6B, hB, and hC, one turn of hD, and the connecting loops (34).…”

Section: Four Amino Acid Residues Within Pedfpep Are Necessary For Inmentioning

confidence: 99%

“…In the vascular endothelial cell system, VEGF and PEDF have counterbalancing proangiogenic and antiangiogenic activities, respectively (17,(19)(20)(21)(22)(23). In motoneurons, both PEDF and VEGF function in concert as neurotrophic͞neuroprotective agents (24)(25)(26)(27). Although the relationships between PEDF and VEGF in angiogenesis and motoneuron survival have been established, it is unknown what effect PEDF has on VEGF's activity in vascular permeability.…”

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confidence: 99%

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Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site

Liu

Ren

Cooper

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

123

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Vascular permeability plays a key role in a wide array of lifethreatening and sight-threatening diseases. Vascular endothelial growth factor can increase vascular permeability. Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability. A 44-amino acid region of PEDF was sufficient to confer the antivasopermeability activity. Additionally, we identified four amino acids (glutamate-101, isoleucine-103, leucine-112, and serine-115) critical for this activity. PEDF, or a derivative, could potentially abate or restore vision loss from diabetic macular edema. Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability.

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“…Negative controls were immunoreacted without primary antibody or with preabsorbed AbrPEDF. Ab-rPEDF was preabsorbed by incubating the antiserum with PEDF protein covalently attached to resin 3M-Emphazed (6 mg rhuPEDF ml 21 resin, and prepared as described by Alberdi et al (1999) for 16 hr at 48C. The resin mixture was transferred to a disposable column and unbound antisera proteins were eluted by gravity flow and collected as preabsorbed Ab-rPEDF.…”

Section: Immunolabelingmentioning

confidence: 99%

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution

Becerra

Fariss

et al. 2004

Experimental Eye Research

114

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Pigment epithelium-derived factor (PEDF) is an extracellular protein derived from the retinal pigment epithelium (RPE), a tissue formed by polarized cells that release growth and trophic factors in a directional fashion. We have investigated the distribution and directional release of PEDF protein by the monkey RPE. We established primary cultures of monkey RPE cells that expressed the PEDF gene, and that synthesized and secreted the PEDF protein. Northern analysis of RPE cultures and monkey ocular tissues showed that PEDF transcripts were highly expressed in RPE as compared with several other monkey ocular tissues, being even more abundant in cultured cells than they were in the native RPE. The differentiated RPE cells in culture secreted protein that shared the immunological, biochemical and biological characteristics of PEDF. The overall PEDF levels in the RPE conditioned media reached 6·5 mg ml 2 after 8 days in culture (i.e. 1·1 pg of PEDF per RPE cell). RPE cells were cultivated on permeable supports as monolayers forming a barrier between apical and basal compartments. Apical and basal culture media were sampled at three or four-day intervals for 18 cycles, and the PEDF content was quantified. Most of the PEDF protein was significantly higher in the apical than in the basal medium (. 4 times) at the initial recovery intervals, to be detected only in the apical medium at the latter intervals. In the native monkey eye, the concentration of soluble PEDF in the interphotoreceptor matrix (144 nM) was 7-fold and 25-fold greater than in vitreous and aqueous, respectively. PEDF was abundant in the interphotoreceptor matrix surrounding rod and cone outer segments, and was detectable at lower levels in the RPE as visualized by confocal microscopy. We concluded that PEDF synthesized by the RPE is secreted preferentially from the apical surface and is distributed apically to the RPE bordering the outer segments of photoreceptors. PEDF can be a useful marker for RPE polarization and differentiation. The polarization of RPE may be an important mechanism to control PEDF secretion and our results offer interesting possibilities on regulation of PEDF. q

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Binding of Pigment Epithelium-derived Factor (PEDF) to Retinoblastoma Cells and Cerebellar Granule Neurons

Cited by 118 publications

References 43 publications

Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor

Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor

Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution

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