Association of p75NTR and α9β1 integrin modulates NGF-dependent cellular responses

Ventresca, Erin M.; Lecht, Shimon; Jakubowski, Piotr; Chiaverelli, Rachel; Weaver, Michael; Valle, Luis Del; Ettinger, Keren; Gincberg, Galit; Priel, Avi; Braiman, Alex; Lazarovici, Philip; Lelkes, Peter I.; Marcinkiewicz, Cezary

doi:10.1016/j.cellsig.2015.02.029

Cited by 16 publications

(14 citation statements)

References 43 publications

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“…The LBC3 cell line was developed from glioblastoma multiforme tissue taken from 56-year-old female patient subjected to surgical tumor resection, and was kindly given to us by Prof. Cezary Marcinkiewicz (Department of Neuroscience, Temple University, Philadelphia, PA, USA) [ 29 ]. The LN-18 and human skin fibroblasts (CRL1474) cell lines were provided by American Type Culture Collection (ATCC).…”

Section: Methodsmentioning

confidence: 99%

The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines

et al. 2017

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Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5–15 nm and 10–20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs. Furthermore, in LBC3 cells treated with 5–15 nm SiNPs we noticed induction of apoptosis and necrosis, while in LN-18 cells only necrosis. The 5–15 nm SiNPs were also found to cause oxidative stress, a loss in mitochondrial membrane potential, and changes in the ultrastructure of the mitochondria in LBC3 cells. Quantitative real-time PCR results showed that in LBC3 cells the mRNA levels of pro-apoptotic genes Bim, Bax, Puma, and Noxa were significantly upregulated. An increase in activity of caspase-9 in these cells was also observed. Moreover, the activation of SiNP-induced autophagy was demonstrated in LBC3 cells as shown by an increase in LC3-II/LC3-I ratio, the upregulation of Atg5 gene and an increase in AVOs-positive cells. In conclusion, this research provides novel information concerning molecular mechanisms of apoptosis and autophagy in LBC3 cells.

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Section: Methodsmentioning

confidence: 99%

The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines

et al. 2017

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“…Histochemical analysis was performed on formalin-fixed, paraffin-embedded tissue as previously described. 26 Tissue sections (5 µm thick) prepared by microtome (RM2255; Leica Microsystems, Wetzlar, Germany) stained for actin cytoskeleton (fluorescein isothiocyanate-phalloidin), nucleus (DAPI), and potentially containing FNDP-(NV) were analyzed in a fluorescence microscope (FSX100; Olympus Corporation, Tokyo, Japan) using green, blue, and red filters, respectively, with 20× and 40× objectives.…”

Section: Tissue Sectioning and Histology Analysismentioning

confidence: 99%

Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)

Barone¹,

Marcinkiewicz²,

Li³

et al. 2018

IJN

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IntroductionWe hereby report on studies aimed to characterize safety, pharmacokinetics, and bio-distribution of fluorescent nanodiamond particles (NV)-Z~800 (FNDP-(NV)) administered to rats by intravenous infusion in a single high dose.MethodsBroad scale biological variables were monitored following acute (90 minutes) and subacute (5 or 14 days) exposure to FNDP-(NV). Primary endpoints included morbidity and mortality, while secondary endpoints focused on hematology and clinical biochemistry biomarkers. Particle distribution (liver, spleen, lung, heart, and kidney) was assessed by whole organ near infrared imaging using an in vivo imaging system. This was validated by the quantification of particles extracted from the same organs and visualized by fluorescent and scanning electron microscopy. FNDP-(NV)-treated rats showed no change in morbidity or mortality and preserved normal motor and sensory function, as assessed by six different tests.ResultsBlood cell counts and plasma biochemistry remained normal. The particles were principally distributed in the liver and spleen. The liver particle load accounted for 51%, 24%, and 18% at 90 minutes, 5 days, and 14 days, respectively. A pilot study of particle clearance from blood indicated 50% clearance 33 minutes following the end of particle infusion.ConclusionWe concluded that systemic exposure of rats to a single high dose of FDNP-(NV)-Z~800 (60 mg/kg) appeared to be safe and well tolerated over at least 2 weeks. These data suggest that FNDP-(NV) should proceed to preclinical development in the near future.

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“…An in vitro “Wound healing” assay (“scratch assay”) was performed as described previously. 25 Briefly, HUVEC were seeded in 12-well plates and maintained for 1–2 days until 80–90% confluency Near-confluent HUVEC cells (monolayer) were subjected to a “gentle scrape” across the plate using a plastic spatula tip, resulting in a gap area (devoid of cells) of approx. 1 mm width and treated or not with FDP-NV for another 24 hrs.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were cultured in 8-wells glass chamber slides and immune-stained, as described previously. 25 The cells were treated (or not) with 0.1 mg/mL of FDP-NV-800nm blocked by BSA in the presence or absence of TPA (see above). A Polyclonal anti-phospho-Erk1/2 antibody (Cell Sign.…”

Section: Immunocytochemistry For the Detection Of Phospho-mapk Erk1/2mentioning

confidence: 99%

<p>Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies</p>

Marcinkiewicz¹,

Lelkes²,

Sternberg³

et al. 2020

NSA

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Background: Recently, we reported the safety and biocompatibility of fluorescent diamond particles, FDP-NV-Z-800nm (FDP-NV) injected intravenously into rats, where no morbidity and mortality were noted over a period of 3 months. The acute effects of FDP-NV-800nm particles on cultured human endothelial and hepatic cells remain unexplored. Purpose: In this study, we aimed to explore select cellular and biochemical functions in cultured human umbilical endothelial cells (HUVEC) and a human hepatic cancer cell line (HepG-2) exposed to FDP-NV-800 in vitro at exposure levels within the pharmacokinetics (Cmax and the nadir) previously reported in vivo. Methods: Diverse cellular and biochemical functions were monitored, which cumulatively can provide insights into some vital cellular functions. Cell proliferation and migration were assessed by quantitative microscopy. Mitochondrial metabolic functions were tested by the MTT assay, and cytosolic esterase activity was studied by the calcein AM assay. Chaperons (CHOP), BiP and apoptosis (caspase-3 activation) were monitored by using Western blot (WB). MAPK Erk1/2 signaling was assessed by the detection of the phosphorylated form of the protein (P-Erk 1/2) and its translocation into the cell nucleus. Results: At all concentrations tested (0.001-0.1mg/mL), FDP-NV did not affect any of the biomarkers of cell integrity of HepG2 cells. In contrast, the proliferation of HUVEC was affected at the highest concentration tested (0.1mg/mL, C max). Exposure of HUVEC to (0.01 mg/mL) FDP-NV had a mild-moderate effect on cell proliferation as evident in the MTT assay and was absent when proliferation was assessed by direct cell counting or by using the calcein AM assays. In both cell types, exposure to the highest concentration (0.1 mg/mL) of FDP-NV did neither affect FBSstimulated cell signaling (MAPK Erk1/2 phosphorylation) nor did it activate of Caspase 3. Conclusion: Our data suggest that FDP-NV-800nm are largely biocompatible with HepG-2 cells proliferation within the pharmacokinetic data reported previously. In contrast, HUVEC proliferation at the highest exposure dose (0.1 mg/mL) responded adversely with respect to several biomarkers of cell integrity. However, since the C max levels are very short-living, the risk for endothelial injury is likely minimal for slow rate cell proliferation such as endothelial cells.

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Association of p75NTR and α9β1 integrin modulates NGF-dependent cellular responses

Cited by 16 publications

References 43 publications

The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines

The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines

Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)

<p>Effects of Fluorescent Diamond Particles FDP-NV-800nm on Essential Biochemical Functions of Primary Human Umbilical Vein Cells and Human Hepatic Cell Line, HepG-2 in vitro (Part VI): Acute Biocompatibility Studies</p>

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