2011
DOI: 10.1007/s10495-011-0678-x
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Peptide-binding GRP78 protects neurons from hypoxia-induced apoptosis

Abstract: Brain ischemia has major consequences leading to the apoptosis of astrocytes and neurons. Glucose-regulated protein 78 (GRP78) known for its role in endoplasmic reticulum stress alleviation was discovered on several cell surfaces acting as a receptor for signaling pathways. We have previously described peptides that bind cell surface GRP78 on endothelial cells to induce angiogenesis. We have also reported that ADoPep1 binds cardiomyocytes to prevent apoptosis of ischemic heart cells. In this study we describe … Show more

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Cited by 35 publications
(31 citation statements)
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“…Thus, under more physiological oxygen concentrations, normal cells present minimal GRP78 on the cell surface and remain unresponsive to BMTP78, whereas tumor cells are in a constant state of stress, regardless of their environment (32). As reported by others (33, 34), growth under hypoxic conditions (1% oxygen) induced a stress response and an increase in surface GRP78 in the two non-transformed lines but had no effect on the two tumor lines (Supplementary Figure 4). …”
Section: Resultssupporting
confidence: 80%
See 1 more Smart Citation
“…Thus, under more physiological oxygen concentrations, normal cells present minimal GRP78 on the cell surface and remain unresponsive to BMTP78, whereas tumor cells are in a constant state of stress, regardless of their environment (32). As reported by others (33, 34), growth under hypoxic conditions (1% oxygen) induced a stress response and an increase in surface GRP78 in the two non-transformed lines but had no effect on the two tumor lines (Supplementary Figure 4). …”
Section: Resultssupporting
confidence: 80%
“…4T1.2 mammary tumors were excised surgically from all mice at ten days post-implantation prior to randomization into three groups (n=15) to receive weekly doses of BMTP78, control peptide or saline. Metastatic cells are present in the lungs at this time (33). BMTP78 treatment significantly extended disease-free survival of the mice (median survival 34 days), compared to either the control peptide (median survival 21 days) or the saline-treated controls (median survival 23 days) (Figure 4F) (p<0.01).…”
Section: Resultsmentioning
confidence: 99%
“…This is a chaperone mainly located at the endoplasmic reticulum (ER) that, alike Hsc70, belongs to the Hsp70 protein family. GRP78 not only is involved in correct protein folding and the assembly of protein complexes in the ER lumen, but also exhibits anti-apoptotic functions in neurons [42]. …”
Section: Resultsmentioning
confidence: 99%
“…In the mouse brain, Pg and t-PA are highly expressed in the hippocampus (10), a region where VDAC expression is also enhanced (11). GRP78 is expressed on the cell surface of human brain glioma cells (12) as well as in mouse brain astrocytes and neurons (13). In our laboratory, we have extensively studied the functions of GRP78 in the cell surface (2), particularly in human prostate cancer (14) and malignant melanoma cells (15).…”
mentioning
confidence: 99%