Activation of the nitric oxide synthase 2 pathway in the response of bone marrow stromal cells to high doses of ionizing radiation

Citation
Nv. Gorbunov et al., Activation of the nitric oxide synthase 2 pathway in the response of bone marrow stromal cells to high doses of ionizing radiation, RADIAT RES, 154(1), 2000, pp. 73-86
Citations number
58
Categorie Soggetti
Experimental Biology
Journal title
RADIATION RESEARCH
ISSN journal
00337587 → ACNP
Volume
154
Issue
1
Year of publication
2000
Pages
73 - 86
Database
ISI
SICI code
0033-7587(200007)154:1<73:AOTNOS>2.0.ZU;2-4
Abstract
Reverse transcription-polymerase chain reaction and immunofluorescence anal ysis of D2XRII murine bone marrow stromal cells showed that gamma irradiati on with doses of 2-50 Gy from Cs-137 stimulated expression of nitric oxide synthase 2 (Nos2, also known as iNos), The activation of Nos2 was accompani ed by an increase in the fluorescence of 4,5-diaminofluorescein diacetate, a nitric oxide trap, and accumulation of 3-nitrotyrosine within cellular pr oteins in a dose-dependent manner. These effects were inhibited by actinomy cin D and by N-[3-(aminomethyl)benzyl]acetamidine dihydrochloride, a specif ic inhibitor of Nos2, The induction of Nos2 expression and Nos2-dependent r elease of nitric oxide in D2XRII cells was observed within 24 h after irrad iation and was similar in magnitude to that observed in cultures incubated with II1b and Tnf, We conducted (1) confocal fluorescence imaging of 3-nitr otyrosine in bone marrow cells of irradiated C57BL/6J mice and (2) 3-nitrot yrosine fluorescence imaging of FDC-P1JL26 hematopoietic cells that were co cultured with previously irradiated D2XRII bone marrow stromal cells. Expos ure to ionizing radiation increased the production of 3-nitro-tyrosine in i rradiated bone marrow cells in vivo and in nonirradiated FDC-P1JL26 cells c ocultured with irradiated D2XRII cells for 1 or 4 h, We suggest that nitrat ive/oxidative stress to the transplanted multilineage hematopoietic cells d ue to exposure to nitric oxide released by host bone marrow stromal cells m ay contribute to the genotoxic events associated with malignant alterations in bone marrow tissue of transplant recipients who are prepared for engraf tment by total-body irradiation. (C) 2000 by Radiation Research Society.