2024-03-28T12:23:11Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/48042023-11-22T12:25:49Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2053com_20.500.12105_2052col_20.500.12105_16977col_20.500.12105_2054
Repisalud
author
López-Nieva, Pilar
author
Malavé, Manuel
author
González-Sánchez, Laura
author
Fernández-Piqueras, José
author
Fernandez-Navarro, Pablo L
author
Santos, Javier
funder
Nuclear Safety Council (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
2017-09-04T16:27:06Z
2017-09-04T16:27:06Z
2016-08-31
BMC Genomics. 2016; 17(1): 698
http://hdl.handle.net/20.500.12105/4804
27581076
10.1186/s12864-016-3036-0
1471-2164
BMC Genomics
BACKGROUND: Radio-Adaptive Response (RAR) is a biological defense mechanism whereby exposure to low dose ionizing radiation (IR) mitigates the detrimental effects of high dose irradiation. RAR has been widely observed in vivo using as endpoint less induction of apoptosis. However, sex differences associated with RAR and variations between males and females on global gene expression influenced by RAR have not been still investigated. In addition, the response to radiation-induced apoptosis is associated with phosphorylation of TRP53 at both the serine 15 (ser-18 in the mouse) and serine 392 (ser-389 in mice) residues, but the role of these two phosphorylated forms in male and female RAR remains to be elucidated.
RESULTS: We analyzed the effect of administering priming low dose radiation (0.075 Gy of X-rays) prior to high dose radiation (1.75 Gy of γ-rays) on the level of caspase-3-mediated apoptosis and on global transcriptional expression in thymocytes of male and female mice. Here, we provide the first evidence of a differential sex effect of RAR on the reduction of thymocyte apoptosis with males showing lesser levels of caspase-3-mediated apoptosis than females. Analysis of transcriptomic profiles of 1944 genes involved in apoptosis signaling in radio-adapted thymocytes identified 17 transcripts exhibiting differential expression between both sexes. Among them, Dlc1 and Fis1 are closely related to the apoptosis mediated by the TRP53 protein. Our data demonstrate that overexpression of Dlc1 and Fis1 occur concomitantly with a highest accumulation of phosphoserine-18-TRP53 and caspase-3 in radio-adapted thymocytes of female mice. In an opposite way, both down-modulation of Fis1 and phosphoserine-389-TRP53 accumulation appear to be associated with protection from thymocyte apoptosis mediated by caspase-3 in males.
CONCLUSIONS: Transcriptomic analysis performed in this work reveals for the first time sex-specific differences in gene expression influenced by RAR. Our results also suggest a sex-dependent dual role for phosphoserine-18-TRP53 and phosphoserine-389-TRP53 in the regulation of the radio-adaptive response in mouse thymocytes.
eng
Radio-adaptive response
Thymocyte apoptosis
Caspase-3
cDNA microarrays
Dlc1
Fis1
Phosphorylation of TRP53 at serine 18 and serine 389
Sex differences
Transcriptomic analysis reveals sex-specific differences in the expression of Dcl1 and Fis1 genes in the radio-adaptive response of thymocytes to TRP53-mediated apoptosis
journal article
URL
https://repisalud.isciii.es/bitstream/20.500.12105/4804/1/TranscriptomicAnalysisRevealsSex_2016.pdf
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TranscriptomicAnalysisRevealsSex_2016.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/4804/20/12864_2016_Article_3036.pdf.txt
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12864_2016_Article_3036.pdf.txt
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https://repisalud.isciii.es/bitstream/20.500.12105/4804/22/TranscriptomicAnalysisRevealsSex_2016.pdf.txt
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TranscriptomicAnalysisRevealsSex_2016.pdf.txt
URL
https://repisalud.isciii.es/bitstream/20.500.12105/4804/26/TranscriptomicAnalysisRevealsSex_2016.pdf.txt
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TranscriptomicAnalysisRevealsSex_2016.pdf.txt