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Open AccessArticle

Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro

1
Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany
2
Department of Veterinary Medicine, Pathology Unit, University of Parma, Strada del Taglio 10, 43126 Parma, Italy
3
Dipartimento di Medicina Veterinaria (DIMEVET), Universitá degli Studi di Milano, Via dell‘Universitá 6, 26900 Lodi, Italy
4
Center for Systems Neuroscience, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
5
Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany
6
Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover; Bünteweg 17, 30559 Hannover, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(2), 200; https://doi.org/10.3390/v12020200 (registering DOI)
Received: 18 December 2019 / Revised: 23 January 2020 / Accepted: 9 February 2020 / Published: 11 February 2020
Histiocytic sarcomas represent malignant tumors which require new treatment strategies. Canine distemper virus (CDV) is a promising candidate due to its oncolytic features reported in a canine histiocytic sarcoma cell line (DH82 cells). Interestingly, the underlying mechanism might include a dysregulation of angiogenesis. Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. Microarray data analysis, immunofluorescence for 8-hydroxyguanosine, superoxide dismutase 2 and catalase, and flow cytometry for oxidative burst displayed an increased oxidative stress in persistently CDV-infected DH82 cells (DH82Ond pi) compared to controls. The HIF-1α expression in DH82Ond pi increased, as demonstrated by Western blot, and showed an unexpected, often sub-membranous distribution, as shown by immunofluorescence and immunoelectron microscopy. Furthermore, microarray data analysis and immunofluorescence confirmed a reduced expression of VEGF-B in DH82Ond pi compared to controls. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress. View Full-Text
Keywords: angiogenesis; canine distemper virus; canine histiocytic sarcoma; DH82; HIF-1α; oxidative stress; VEGF-B; viral oncolysis angiogenesis; canine distemper virus; canine histiocytic sarcoma; DH82; HIF-1α; oxidative stress; VEGF-B; viral oncolysis
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Armando, F.; Gambini, M.; Corradi, A.; Giudice, C.; Pfankuche, V.M.; Brogden, G.; Attig, F.; von Köckritz-Blickwede, M.; Baumgärtner, W.; Puff, C. Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro. Viruses 2020, 12, 200.

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