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Induction of a radio‐adaptive response by low‐dose gamma irradiation in mouse cardiac myocytes
Author(s) -
Seawright John,
Westby Christian M.,
Wu Honglu
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1085.2
Subject(s) - sod2 , oxidative stress , myocyte , fibrosis , downregulation and upregulation , apoptosis , cardiac fibrosis , medicine , biology , gpx4 , cancer research , andrology , gene , superoxide dismutase , genetics , glutathione peroxidase
In addition to cancer, astronauts may be at risk for radiation‐induced cardiovascular diseases. While it is believed that these radiation‐induced disorders are a result of abnormal tissue remodeling, the mechanisms remain unclear. We assessed the expression and radio‐adaptive response of genes associated with fibrosis, apoptosis, and oxidative and inflammatory stress in cardiac myocytes. Seven week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137 Cs γ radiation and sacrificed 4, 24, or 72hr after final irradiation. Using RT‐PCR, the expression of pro‐apoptotic Bad and Bax, procell survival Bcl2 and Bcl2l2, fibrosis Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,‐6; Bax,‐7; Bcl2,‐5; Bcl2l2,‐4; Vegfa, −12; Sod2,‐6; GPx4,‐ 29) 4h after H compared to control. Regulation of Casp3, Casp9, Trp53, and Myc also trended downward but did not achieve statistical significance. 24hr after H, genetic down‐regulation was no longer present. The genetic expression in the 4h LH group was similar to control. These data suggest that the effect of a single high dose of radiation on cardiac myocytes is short lived but can be prevented by pre‐exposure to a much lower dose. This knowledge may serve to guide the development of countermeasures to preserve the cardiovascular health of astronauts. Support: NASA, Johnson Space Center Human Research Project