PACAP and VIP affect NF1 expression in rat malignant peripheral nerve sheath tumor (MPNST) cells

Giunta, Salvatore; Castorina, Alessandro; Adorno, A.; Mazzone, Venera; Carnazza, Maria Luisa; D’Agata, Velia

doi:10.1016/j.npep.2009.10.003

Cited by 25 publications

(18 citation statements)

References 56 publications

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“…6). In agreement with our previous work (8), MPNST cells cultured in presence of normal levels of serum displayed a low intense immunosignal, which raised significantly in serum-deprived cells after 48 h. The addition of 0.1% DMSO (vehicle) in the absence of serum did not produce appreciable changes on neurofibromin reactivity. Treatment with 10 -5 M D 3 R agonist induced a notable reduction of the immunosignal as compared to serum-starved cells added with vehicle only after 48 h exposure (Fig.…”

Section: Neurofibromin Immunofluorescence Analysis In Mpnst Cells Tresupporting

confidence: 92%

“…Our research group has previously shown that serumstarved MPNST cells undergo apoptosis (25) Thereafter, we have correlated this effect to changes in the expression of the NF1 tumor suppressor gene, suggesting that besides its Rasdependent control on cell proliferation (26,27), NF1 might exert tumor suppression by conferring sensitivity to apoptosis (7,8). Interestingly, a functional link between the D 3 R and neurofibromin have been proposed, corroborating the idea that D 3 Rs might mediate a protective action after serum deprivation in MPNST cells through the interaction with the NF1 gene (18).…”

Section: Discussionmentioning

confidence: 86%

“…Neurofibromin acts as a GAP, which terminates Ras signalling. In addition to its role in controlling cell proliferation, a proapoptotic role of neurofibromin has been proposed in mouse embryonic fibroblasts (7) and in MPNST cells (8), suggesting that besides its Ras-dependent growth inhibition, neurofibromin may exert tumor suppression by conferring sensitivity to apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…However, the cellular mechanisms for protection triggered by D 3 Rs remain unexplored. The previous identification of a functional correlation between the D 3 R and neurofibromin (18) and the subsequent proposals of NF1 as a candidate proapoptotic gene (7,8) led us to hypothesize that the D 3 R might also mediate a protective action in response to serum deprivation in MPNST cells, possibly through the interaction with neurofibromin. To test this hypothesis, the biological role of the selective D 3 R agonist 7-OH-PIPAT was assessed in serum-starved MPNST cells and the effect was correlated to changes in NF1 expression.…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of the dopamine D3 receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells

Castorina

Giunta²,

D’Agata³

2010

Int J Oncol

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Abstract. Emerging evidence indicates that the dopamine D 3 receptor (D 3 R) mediates protective roles both in neuronal and non-neuronal cell lines. In a previous study we proposed that neurofibromin, a large tumor suppressor protein encoded by the neurofibromatosis type 1 gene (NF1), may increase susceptibility to apoptosis after serum deprivation in malignant peripheral nerve sheath tumor (MPNST) cells, thus acting as a proapoptotic gene. In addition, it has been observed that D 3 Rs are functionally correlated to neurofibromin. In this study, we examined whether 7-OH-PIPAT, a potent dopamine D 3 R agonist, exerts an antiapoptotic role under the same culture conditions and then correlated this effect to changes in NF1 expression. Results showed that serum deprivation caused a significant reduction of cell viability (MTT assay) both after 24 and 48 h (p<0.001). Treatment with increasing concentrations of 7-OH-PIPAT (10 -9 -10 -5 M) induced a progressive increase in cell viability both after 24 and 48 h as compared to vehicle-treated cells, with significant changes at the highest concentrations tested (10 -6 and 10 -5 M). Consistently, at the latter two concentrations, a significant reduction in oligonucleosomes formation was observed, thus suggesting an antiapoptotic role of 7-OH-PIPAT. These results were confirmed by Hoechst 33254 nuclear staining. To investigate whether these effects were correlated to changes in NF1 transcript and protein expression, quantitative realtime PCR, Western blot and immunofluorescence analyses were performed. Results demonstrated that the upregulation of NF1 transcripts and protein levels induced by serum withdrawal were remarkably attenuated by 10 -6 and 10 -5 M agonist treatment within 24 h (p<0.01 and p<0.001, respectively), whereas similar effects were observed already at a lower concentration (10 -7 M) after 48 h treatment (p<0.001). In conclusion, these results suggest that D 3 R might mediate the protective response to serum deprivation in MPNST cells through the inhibition of NF1 gene expression, further underlying a subtle role of these receptors in MPNST development.

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Section: Neurofibromin Immunofluorescence Analysis In Mpnst Cells Tresupporting

confidence: 92%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protective effect of the dopamine D3 receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells

Castorina

Giunta²,

D’Agata³

2010

Int J Oncol

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“…In the CNS, they act as neurotransmitters and neuromodulators, but are also involved in regulating processes such as cell division, neuronal differentiation, embryonic development, and neuronal survival [14,35,37]. In the PNS, they exert both neuro-and glio-protective actions against various type of insults [8,7,13], and endogenous peptides have been shown to mediate pro-regenerating effects after peripheral nerve injuries in vivo, where overexpression is observed at the level of the injury site [31]. From another study it has emerged that local administration of VIP accelerates early myelination and growth of regenerating axons after sciatic nerve transection [39].…”

Section: Introductionmentioning

confidence: 99%

PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: Involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways

Castorina

Scuderi

D’Amico

et al. 2014

Experimental Cell Research

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VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of Diabetic Macular Edema

Maugeri

D’Amico

Gagliano³

et al. 2016

Journal Cellular Physiology

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Diabetic macular edema (DME), characterized by an increase of thickness in the eye macular area, is due to breakdown of the blood-retinal barrier (BRB). Hypoxia plays a key role in the progression of this pathology by activating the hypoxia-inducible factors. In the last years, various studies have put their attention on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in retinal dysfunction. However, until now, no study has investigated their protective role against the harmful combined effect of both hyperglycemia and hypoxia on outer BRB. Therefore, in the present study, we have analyzed the role of these peptides on permeability, restoration of tight junctions expression and inhibition of hyperglycemia/hypoxia-induced apoptosis, in an experimental in vitro model of outer BRB. Our results have demonstrated that the peptides' treatment have restored the integrity of outer BRB induced by cell exposure to hyperglycemia/hypoxia. Their effect is mediated through the activation of phosphoinositide 3 kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling pathways. In conclusion, our study further clarifies the mechanism through which PACAP and VIP perform the beneficial effect on retinal damage induced by hyperglycemic/hypoxic insult, responsible of DME progression. J. Cell. Physiol. 232: 1079-1085, 2017. © 2016 Wiley Periodicals, Inc.

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PACAP and VIP affect NF1 expression in rat malignant peripheral nerve sheath tumor (MPNST) cells

Cited by 25 publications

References 56 publications

Protective effect of the dopamine D3 receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells

Protective effect of the dopamine D3 receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells

PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: Involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways

VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of Diabetic Macular Edema

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