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21.
Annamaria Spina Luca Sorvillo Francesca Di Maiolo Antonietta Esposito Raffaella D'Auria Davide Di Gesto Emilio Chiosi Silvio Naviglio 《Journal of cellular physiology》2013,228(1):198-206
Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. The clinical outcome for osteosarcoma remains discouraging despite aggressive surgery and intensive radiotherapy and chemotherapy regimens. Thus, novel therapeutic approaches are needed. Previously, we have shown that inorganic phosphate (Pi) inhibits proliferation and aggressiveness of human osteosarcoma U2OS cells identifying adenylate cyclase, beta3 integrin, Rap1, ERK1/2 as proteins whose expression and function are relevantly affected in response to Pi. In this study, we investigated whether Pi could affect chemosensitivity of osteosarcoma cells and the underlying molecular mechanisms. Here, we report that Pi inhibits proliferation of p53‐wild type U2OS cells (and not of p53‐null Saos and p53‐mutant MG63 cells) by slowing‐down cell cycle progression, without apoptosis occurrence. Interestingly, we found that Pi strongly enhances doxorubicin‐induced cytotoxicity in U2OS, and not in Saos and MG63 cells, by apoptosis induction, as revealed by a marked increase of sub‐G1 population, Bcl‐2 downregulation, caspase‐3 activation, and PARP cleavage. Remarkably, Pi/doxorubicin combination‐induced cytotoxicity was accompanied by an increase of p53 protein levels and of p53 target genes mdm2, p21 and Bax, and was significantly reduced by the p53 inhibitor pifithrine‐alpha. Moreover, the doxorubicin‐induced cytotoxicity was associated with ERK1/2 pathway inhibition in response to Pi. Altogether, our data enforce the evidence of Pi as a novel signaling molecule capable of inhibiting ERK pathway and inducing sensitization to doxorubicin of osteosarcoma cells by p53‐dependent apoptosis, implying that targeting Pi levels might represent a rational strategy for improving osteosarcoma therapy. J. Cell. Physiol. 228: 198–206, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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Carlotta Giromini Raffaella Rebucci Eleonora Fusi Luciana Rossi Francesca Saccone Antonella Baldi 《Cell biology and toxicology》2016,32(3):249-258
This study aimed to investigate the in vitro damage induced by ochratoxin A (OTA) in BME-UV1 and MDCK epithelial cells. Both cells lines were treated with OTA (0 up to 10 μg/mL), and cell viability (MTT assay), membrane stability (lactate dehydrogenase (LDH) release assay) and apoptotic cell rate (Tunel assay) were investigated. Further, the effect of the incubation with OTA has been evaluated at DNA level by the determination of DNA integrity, by the quantification of DNA adduct formation (8-hydroxy-2′-deoxyguanosine (8-OHdG)) and by the assessment of the global DNA methylation status (5-methyl-cytosine (5-mC)). The obtained results showed that after 24 h of OTA treatment, BME-UV1 cell viability was reduced in a dose-dependent way. OTA significantly (P?<?0.05) increased LDH release in BME-UV1 cells at all concentrations tested. OTA (1.25 μg/mL) induced 35 % LDH release in MDCK cells (P?<?0.05). A significant (P?<?0.05) change in percentages of apoptotic BME-UV1 (10?±?0.86) and MDCK (25?±?0.88) cells was calculated when the cells were co-incubated with OTA. The level of 8-OHdG adduct formation was significantly (P?<?0.05) increased in BME-UV1 cells treated with 1.25 μg/mL of OTA. The results of the present study suggest that a different mechanism of action may occur in these cell lines. 相似文献
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Amin Soltangheisi Paul J. A. Withers Paulo Sergio Pavinato Maurício Roberto Cherubin Raffaella Rossetto Janaina Braga Do Carmo Gustavo Casoni da Rocha Luiz Antonio Martinelli 《Global Change Biology Bioenergy》2019,11(12):1444-1455
Phosphorus (P) use in global food and bioenergy production needs to become more efficient and sustainable to reduce environmental impacts and conserve a finite and critical resource (Carpenter & Bennett, Environmental Research Letters, 2011, 6, 014009; Springmann et al., Nature, 2018, 562, 519). Sugarcane is one crop with a large P footprint because production is centered on P‐fixing soils with low P availability (Roy et al., Nature Plants, 2016, 2, 16043; Withers et al., Scientific Reports, 2018, 8, 2537). As global demand for processed sugar and bioethanol continues to increase, we advocate that improving P efficiency could become a key sustainability goal for the sugarcane industry. Here, we applied the 5R global P stewardship framework (Withers et al., Ambio, 2015, 44, 193) to identify more sustainable options to manage P in Brazilian sugarcane production. We show that current inputs of P fertilizer to the current crop area could be reduced by over 305 Gg, or 63%, over the next three decades by reducing unnecessary P fertilizer use, better utilization of recyclable bioresources and redesigning recommendation systems. Adoption of these 5R options would save the sugarcane industry in Brazil 528 US$ million and help safeguard global food and energy security. 相似文献
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Roberta Piazza Filippo Micheletti Sara Condino Giada Magni Raffaella N. Berchiolli Paolo De Simone Vincenzo Ferrari Mauro Ferrari Roberto Pini Francesca Rossi 《Journal of biophotonics》2019,12(9)
The in situ laser fenestration is an interesting option for the endovascular treatment of short‐necked aneurysms with an intraoperative modification of a standard endograft. According to literature evidence, diode laser emitting in the near‐infrared wavelength (810 nm) can be successfully used to fenestrate the endograft fabric. This paper describes a three‐dimensional navigation system for the accurate targeting of the fenestration site, then reports results of an ex vivo study to assess whether the laser operative conditions, which ensure the fabric fenestration, are harmless for the biological tissue surrounding the endoprosthesis. Two hundred twenty‐five samples of human aorta, including healthy specimens and abdominal aortic aneurysm samples, were irradiated ex vivo using a 810 nm diode laser. Energy and pulse duration were varied. Irradiated tissues were fixed in formaldehyde, sectioned and subjected to histological examination. Only 7.5% of the irradiated samples exhibited a thermal damage, which was always confined to the contact point between the laser fiber tip and the aortic wall. These experiments suggest that the diode laser can be safely used for the proposed surgical application. 相似文献
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Giulia Schiroli Anastasia Conti Samuele Ferrari Lucrezia della Volpe Aurelien Jacob Luisa Albano Stefano Beretta Andrea Calabria Valentina Vavassori Patrizia Gasparini Eralda Salataj Delphine Ndiaye-Lobry Chiara Brombin Julie Chaumeil Eugenio Montini Ivan Merelli Pietro Genovese Luigi Naldini Raffaella Di Micco 《Cell Stem Cell》2019,24(4):551-565.e8
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Blood coagulation factor V circulates as a procofactor with little or no procoagulant activity. It is activated to factor Va by thrombin following proteolytic removal of a large central B-domain. Although this reaction is well studied, the mechanism by which bond cleavage and B-domain release facilitate the transition to the active cofactor state has not been defined. Here we show that deletion or substitution of specific B-domain sequences drives the expression of procoagulant function without the need for proteolytic processing. Conversion to the constitutively active cofactor state is related, at least in part, to a cluster of amino acids that is highly basic and well conserved across the vertebrate lineage. Our findings demonstrate that discrete sequences in the B-domain serve to stabilize the inactive procofactor state, with proteolysis primarily functioning to remove these inhibitory constraints. These unexpected results provide new insight into the mechanism of factor V activation. 相似文献
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