Gamma-tocotrienol (GT3), a naturally occurring vitamin E isomer, a promising radioprotector, has been shown to protect mice against radiation-induced hematopoietic and gastrointestinal injuries. We analyzed changes in protein expression profiles of spleen tissue after GT3 treatment in mice exposed to gamma radiation to gain insights into the molecular mechanism of radioprotective efficacy. Male CD2F1 mice, 12-to-14 weeks old, were treated with either vehicle or GT3 at 24 h prior to 7 Gy total-body irradiation. Nonirradiated vehicle, nonirradiated GT3 and age-matched naïve animals were used as controls. Blood and tissues were harvested on days 0, 1, 2, 4, 7, 10 and 14 postirradiation. High-resolution mass-spectrometry-based radioproteomics was used to identify differentially expressed proteins in spleen tissue with or without drug treatment. Subsequent bioinformatic analyses helped delineate molecular markers of biological pathways and networks regulating the cellular radiation responses in spleen. Our results show a robust alteration in spleen proteomic profiles including upregulation of the Wnt signaling pathway and actin-cytoskeleton linked proteins in mediating the radiation injury response in spleen. Furthermore, we show that 24 h pretreatment with GT3 attenuates radiation-induced hematopoietic injury in the spleen by modulating various cell signaling proteins. Taken together, our results show that the radioprotective effects of GT3 are mediated, via alleviation of radiation-induced alterations in biochemical pathways, with wide implications on overall hematopoietic injury.
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1 November 2018
Research Article|
August 02 2018
Proteomic Changes in Mouse Spleen after Radiation-Induced Injury and its Modulation by Gamma-Tocotrienol
Amrita K. Cheema;
Amrita K. Cheema
aDepartments of Oncology, Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC
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Stephanie D. Byrum;
Stephanie D. Byrum
bDivision of Radiation Health, College of Pharmacy, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas
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Neel Kamal Sharma;
Neel Kamal Sharma
1
cArmed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland
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Tatiana Altadill;
Tatiana Altadill
aDepartments of Oncology, Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC
dInstitut d'Investigacio Biomedica de Bellvitge (IDIBELL), Gynecological Department, Vall Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain
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Vidya P. Kumar;
Vidya P. Kumar
1
cArmed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland
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Shukla Biswas;
Shukla Biswas
cArmed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland
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Brian M. Balgley;
Brian M. Balgley
eBioproximity, LLC, Chantilly Virginia
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Martin Hauer-Jensen;
Martin Hauer-Jensen
bDivision of Radiation Health, College of Pharmacy, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas
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Alan J. Tackett;
Alan J. Tackett
bDivision of Radiation Health, College of Pharmacy, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas
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Sanchita P. Ghosh
Sanchita P. Ghosh
2
cArmed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland
2Address correspondence: Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Ave, Bldg. 42, Bethesda, Maryland 20889; email: sanchita.ghosh@usuhs.edu.
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Radiat Res (2018) 190 (5): 449–463.
Citation
Amrita K. Cheema, Stephanie D. Byrum, Neel Kamal Sharma, Tatiana Altadill, Vidya P. Kumar, Shukla Biswas, Brian M. Balgley, Martin Hauer-Jensen, Alan J. Tackett, Sanchita P. Ghosh; Proteomic Changes in Mouse Spleen after Radiation-Induced Injury and its Modulation by Gamma-Tocotrienol. Radiat Res 1 November 2018; 190 (5): 449–463. doi: https://doi.org/10.1667/RR15008.1
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