Pigment Epithelium-derived Factor (PEDF) Protects Motor Neurons from Chronic Glutamate-mediated Neurodegeneration

Bilak, Masako M.; Corse, Andrea M.; Bilak, Stephan R.; Lehar, Mohamed; Tombran-Tink, Joyce; Kuncl, Ralph W.

doi:10.1097/00005072-199907000-00006

Cited by 161 publications

(129 citation statements)

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“…exhibits neuronal differentiating activity on human retinoblastoma cells (Fig. 4) and is protective for motor neurons against chronic glutamate toxicity in organotypic spinal cord cultures (8). These observations suggest that the region spanning positions 78 -121 is the site in PEDF that binds to receptors on Y-79 cells.…”

Section: Discussionmentioning

confidence: 86%

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

Alberdi¹,

Aymerich

Becerra

1999

Journal of Biological Chemistry

117

127

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Section: Discussionmentioning

confidence: 86%

“…Recent reports indicate that it has effects on other types of neurons. It promotes the survival and differentiation of developing spinal motor neurons (7), and can protect them against glutamate neurodegeneration (8). PEDF can also protect developing primary hippocampal neurons against glutamate neurotoxicity (9).…”

mentioning

confidence: 99%

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

Alberdi¹,

Aymerich

Becerra

1999

Journal of Biological Chemistry

117

127

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“…Araki et al 25 found that the death of CGCs occurred mostly by ''natural apoptosis'' but not by PEDF induction. Nevertheless, Bilek et al 10 showed that PEDF was effective in protecting the neurons against neurotoxins, such as glutamate. 26 From these studies, it raises controversy as to the action of PEDF in antiapoptosis of CGCs and neurons and proapoptosis in glioma cells.…”

Section: Discussionmentioning

confidence: 99%

“…9 Several clinical and laboratory studies have shown that the ''gliastatic'' effect of PEDF, along with the neuronsurvival character, could be of benefit in the management of some diseases related to the central nervous system. [10][11][12] However, little is known about the effect of PEDF on the growth and invasion of glioma, which constitutes the majority of primary brain tumors.…”

mentioning

confidence: 99%

Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor

et al. 2004

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Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis and an inducer of neural differentiation. We previously reported the loss of PEDF expression in glioma progression. In this study, we investigated whether PEDF overexpression could suppress glioma growth and invasion. Glioma cell line U251 was stably transfected with a full-length human PEDF expression vector. The expression and release of various cytokines and angiogenic factors into the medium were analyzed by realtime reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and gelatin zymography. Apoptosis was checked by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Growth inhibition was evaluated by using the in vitro Matrigel invasion. Tumorigenicity was examined in vivo by subcutaneous xenotransplantation into severe combined immunodeficient mice. In U251 cells overexpressing PEDF, thrombospondin-1 protein was upregulated (5.3-fold more), but the production of vascular endothelial growth factor (VEGF) (1.8-fold less) and basic fibroblast growth factor (2.5-fold less) was lower than in cells transfected with the vector only. PEDF also downregulated the production of matrix metalloproteinase-9. Conditioned medium collected from the PEDF-transfected U251 cells showed a significant reduction of VEGF expression. In vitro invasiveness was reduced by approximately 40%. PEDF expression prevented the growth of transfected cells and caused a significant increase in the percentage of cells undergoing apoptosis (50.4% in PEDF-transfected cells). Furthermore, the size of xenotransplants was significantly smaller. In conclusion, PEDF overexpression decreased malignancy, and this might be attributed to the promotion of apoptosis and the regulation of expression of angiogenic effectors. Thus, treatment with PEDF may be useful in patients with malignant gliomas. However, the mechanism of apoptosis induction needs to be investigated.

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“…11,12 Since its discovery, PEDF's role as a neurotrophic and anti-angiogenic factor has been well-defined. 13,14 Studies have subsequently determined that PEDF has a broad range of functions, including immumodulation, 15,16 anti-fibrosis and protection from oxidative stress. 17,18 Compared to other anti-angiogenic factors such as angiostatin and endostatin, PEDF has been shown to be more potent in its anti-angiogenic activity.…”

mentioning

confidence: 99%

PEDF as a treatment for cervical cancer

Murray¹,

Xing²

2010

Cancer Biology & Therapy

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Pigment Epithelium-derived Factor (PEDF) Protects Motor Neurons from Chronic Glutamate-mediated Neurodegeneration

Cited by 161 publications

References 0 publications

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

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

Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor

PEDF as a treatment for cervical cancer

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