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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Phosphorylation and cytoplasmic localization of MAPK p38 during apoptosis signaling in bone marrow granulocytes of mice irradiated in vivo and the role of amifostine in reducing these effects

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Author(s):
Segreto, Helena R. C. [1] ; Oshima, Celina T. F. [2] ; Franco, Marcello F. [2] ; Silva, Maria Regina R. [2] ; Egami, Mizue I. [3] ; Teixeira, Vicente P. C. [2] ; Segreto, Roberto A. [1]
Total Authors: 7
Affiliation:
[1] Univ Fed Sao Paulo, Dept Clin & Expt Oncol, Div Radiotherapy, BR-04616002 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Pathol, BR-04616002 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Morphol, BR-04616002 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: ACTA HISTOCHEMICA; v. 113, n. 3, p. 300-307, 2011.
Web of Science Citations: 8
Abstract

We studied p38 phosphorylation and its intracellular localization during p53 and Puma (a p53 upregulated modulator of apoptosis) apoptotic signaling pathway in bone marrow granulocytes in mice irradiated in vivo and the role of the radioprotector amifostine in ameliorating these responses. Sixty-four C578L mice were randomly assigned in two non-irradiated (Ami-/rad - and Ami +/rad -) and two irradiated (Ami - /rad + and Ami +/rad +) groups. Animals received 400 mg/kg of amifostine i.p. 30 min prior to a single whole body radiation dose of 7 Gy. The experiments were performed using immunohistochemistry for caspase-3, cleaved caspase-3, p53, p-p53 (Ser 15), Puma, p38 and p-p38 (Thr 180/Tyr 182) protein expression. In addition transmission electron microscopy was used for ultrastructural characterization of apoptosis. Data showed that: (i) amifostine significantly reduced the number of apoptotic cells, (ii) p-p53 and Puma proteins were strongly immunostained in granulocytes after irradiation (Ami - /rad +), (iii) amifostine decreased the immunostaining of the proteins (Ami +/rad +), (iv) p38 was immunolocalized in physiological conditions in the nucleus and cytoplasm of granulocytes and neither radiation nor amifostine changed the protein immunostaining or its subcellular distribution, but influenced its activation, (v) radiation-induced p38 phosphorylation and its cytoplasmic accumulation during apoptosis signaling in granulocytes after whole body high radiation dose and amifostine markedly reduced these effects. (C) 2010 Elsevier GmbH. All rights reserved. (AU)