Sortilin Expression Is Essential for Pro-Nerve Growth Factor-Induced Apoptosis of Rat Vascular Smooth Muscle Cells

Campagnolo, Luisa; Costanza, Gaetana; Francesconi, Arianna; Arcuri, Gaetano; Moscatelli, Ilana; Orlandi, Augusto

doi:10.1371/journal.pone.0084969

Cited by 30 publications

(22 citation statements)

References 37 publications

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“…Actions of proNGF and NGF are initiated upon receptor binding and the receptor molecules linked to proNGF-inducible cell death in brain, namely p75 NTR and sortilin, are present in cultured GCs, in addition to TrkA. The cellular localization of sortilin appears to be related to its function, as suggested recently [41]. If so, the intracellular localization, rather than membrane-associated localization of sortilin in GCs seen in our study may provide a possible explanation for a lack of proNGF activity in GCs.…”

Section: Discussionmentioning

confidence: 81%

Pro-nerve growth factor in the ovary and human granulosa cells

Meinel

Blohberger

Berg

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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Background Pro-nerve growth factor must be cleaved to generate mature NGF, which was suggested to be a factor involved in ovarian physiology and pathology. Extracellular proNGF can induce cell death in many tissues. Whether extracellular proNGF exists in the ovary and may play a role in the death of follicular cells or atresia was unknown. Material and Methods Immunohistochemistry of human and Rhesus monkey ovarian sections was performed. IVF-derived follicular fluid and human granulosa cells were studied by RT-PCR, qPCR, Western blotting, ATP- and caspase-assays. Results and Conclusions Immunohistochemistry of ovarian sections identified proNGF in granulosa cells and Western blotting of human isolated granulosa cells confirmed the presence of proNGF. Ovarian granulosa cells thus produce proNGF. Recombinant human proNGF even at high concentrations did not affect the levels of ATP or the activity of caspase 3/7, indicating that in granulosa cells proNGF does not induce death. In contrast, mature NGF, which was detected previously in follicular fluid, may be a trophic molecule for granulosa cells with unexpected functions. We found that in contrast to proNGF, NGF increased the levels of the transcription factor early growth response 1 and of the enzyme choline acetyl-transferase. A mechanism for the generation of mature NGF from proNGF in the follicular fluid may be extracellular enzymatic cleavage. The enzyme MMP7 is known to cleave proNGF and was identified in follicular fluid and as a product of granulosa cells. Thus the generation of NGF in the ovarian follicle may depend on MMP7.

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Section: Discussionmentioning

confidence: 81%

Pro-nerve growth factor in the ovary and human granulosa cells

Meinel

Blohberger

Berg

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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“…The total protein extracts were isolated using lysis buffer and quantified by the Bradford assay [31]. Aliquots (70 µg total protein/sample) were separated by gradient sodium dodecyl sulfate polyacrylamide gel electrophoresis and blotted to nitrocellulose transfer membranes (GE Healthcare Europe GmbH).…”

Section: Methodsmentioning

confidence: 99%

Antioxidant Treatment Prevents Serum Deprivation- and TNF-α-Induced Endothelial Dysfunction through the Inhibition of NADPH Oxidase 4 and the Restoration of β-Oxidation

Bielli¹,

Agostinelli²,

Tarquini³

et al. 2014

J Vasc Res

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Aims: Oxidative stress plays a pivotal role in the impaired endothelial function occurring in vascular diseases. Antioxidant strategies induce a clinical advantage in patients with endothelial dysfunction and atherosclerosis and protect from oxidative damage, but the underlying molecular mechanisms have been poorly evaluated. The aim of this study was to analyze the effects and mechanisms of action of antioxidant regimens on endothelial function. Methods and Results: Antioxidant efficacy of N-acetylcysteine, ascorbic acid and propionyl-L-carnitine was evaluated in serum-deprived and TNF-α-stimulated human umbilical vein endothelial cells in vitro. Cell adhesion molecule (CAM) expression was evaluated by blot and real-time PCR, and inflammatory cytokine secretion was evaluated by ELISA; leukocyte adhesion and reactive oxygen species assays and NADPH oxidase 4 isoform (Nox4) expression analyses by blots were also performed. Antioxidant pretreatment restored serum-deprived and TNF-α-induced impaired mitochondrial β-oxidation by reducing flavin adenine dinucleotide level and counteracting increased CAM and Nox4 expression, leukocyte adhesion and inflammatory cytokine secretion. Specific inhibition by plumbagin and siNox4 prevented TNF-α- and serum deprivation-induced detrimental effects, confirming that endothelial oxidative stress and inflammation were Nox4 dependent. Conclusions: Our findings documented Nox4 as a main actor in oxidative stress-induced endothelial dysfunction and further clarify the molecular basis of antioxidant treatment efficacy. © 2014 S. Karger AG, Basel

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“…Furthermore, ASCs secrete hepatocyte growth factor, tumor necrosis factor-α and nerve growth factor (Salgado et al 2010). Nerve growth factor and precursors are capable of inducing vascular remodeling by modulating vascular cells apoptotic sensitivity (Campagnolo et al 2014). …”

Section: Adipose-derived Stem Cells and Angiogenesismentioning

confidence: 99%

Adult adipose-derived stem cells and breast cancer: a controversial relationship

et al. 2014

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Breast cancer is the most common cancer in women and autologous fat grafting is an important clinical application in treatment of post-surgical deformities. The simplicity of fat grafting procedures and the absence of subsequent visible scar prompted an increasing interest for this technique. The plasticity of adipose-derived stem cells (ASCs) obtained from stromal vascular fraction (SVF) of adult adipose tissue provided exciting perspectives for regenerative medicine and surgery. The recent discovery that SVF/ASC enrichment further ameliorates clinical efficacy of grafting ASCs suggest as ASC-mediated new adipogenesis and vasculogenesis. ASC adipogenic differentiation involves Akt activity and EGFRs, FGFRs, ERbB2 receptor-mediated pathways that also play a pivotal role in the regulation of breast cancer growth. Moreover, the finding that platelet-derived growth factors and hormones improved long-term maintenance of fat grafting raises new concerns for their use during breast reconstruction after cancer surgery. However, it remains unclear whether grafted or resident ASCs may increase the risk of de novo cancer development or recurrence. Preliminary follow-up studies seem to support the efficacy and safety of SVF/ASCs enrichment and the additional benefit from the combined use of autologous platelet-derived growth factors and hormones during breast reconstruction procedures. In the present review we highlighted the complex interplay between resident or grafted ASCs, mature adipocytes, dormant or active breast cancer cells and tumor microenvironment. Actually, data concerning the permissive role of ASCs on breast cancer progression are contrasting, although no clear evidence speaking against their use exists.

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Sortilin Expression Is Essential for Pro-Nerve Growth Factor-Induced Apoptosis of Rat Vascular Smooth Muscle Cells

Cited by 30 publications

References 37 publications

Pro-nerve growth factor in the ovary and human granulosa cells

Pro-nerve growth factor in the ovary and human granulosa cells

Antioxidant Treatment Prevents Serum Deprivation- and TNF-α-Induced Endothelial Dysfunction through the Inhibition of NADPH Oxidase 4 and the Restoration of β-Oxidation

Adult adipose-derived stem cells and breast cancer: a controversial relationship

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