Page 148 - 2014 Printable Abstract Book
P. 148
acute leukemia cell lines through ERK1/2 pathway, and miR-27b may function as a tumor suppressor that
inhibits cell proliferation and induces S phase arrest via targeting cyclin A2.
(PS2-21) PPAR alpha: a key regulator of progressive metabolic changes after neonatal total body low-
1
1
1
dose ionizing radiation. Mayur V. Bakshi ; Omid Azimzadeh, PhD ; Zarko Barjaktarovic, PhD ; Stefan J.
2
1
3
3
1
Kempf ; Juliane Merl, PhD ; Sonja Buratovic ; Per Eriksson, PhD ; Micheal J. Atkinson, PhD ; and Soile
1
1
Tapio, PhD, Inst. of Radiation Biology, Helmholtz Center Munich, Neuherberg, Germany ; Research Unit
2
Protein Science, Helmholtz Center Munich, Nuherberg, Germany ; and Department of Environmental
3
Toxicology, Uppsala University, Uppsala, Sweden
Effects of low-dose total body ionizing radiation are becoming a major cause of concern for
radiation protection. Epidemiological studies have shown that children and young adults are especially
susceptible to radiation-induced cardiovascular disease (CVD). Long-term effects of low and moderate
doses of ionizing radiation target the metabolic system directly or indirectly, especially when the body
60
needs adaptation to metabolic tuning. In this study NMRI mice received single doses of total body Co
137
or Cs gamma-irradiation on postnatal day (PND) 10 and were sacrificed either at PND 11 or 7 months
post-irradiation. The doses used were 0.02/0.05, 0.10, 0.50 and 1.0 Gy. Changes in cardiac and liver
protein expression were quantified using Isotope Coded Protein Label (ICPL) and tandem mass
spectrometry (LC-MS/MS). Progressive structural and metabolic impairments were observed in both
organs. We observed decrease in pyruvate metabolism in liver and shock response (dose dependent up-
++
regulation of Ca ATPases Atp2a2) in heart as immediate responses on PND 11. Interestingly, the
transcription factor peroxisome proliferator-activated receptor (PPAR) alpha was found to be activated in
heart and deactivated in liver after 7 months. Inflammatory processes that are partly regulated by PPAR
alpha were found to be affected in both organs at all doses and time points. These observations were
proven by immuno-blotting and activity assays. PPAR alpha is an essential transcription factor involved in
metabolic adaptations in neonates, especially for lipid metabolic processes. This study highlights PPAR
alpha as the long-term key regulator of metabolic homeostasis after exposure to low and moderate dose
ionizing radiation in neonatal stage. Reference: Bakshi MV, et al. Long-term effects of acute low-dose
ionizing radiation on the neonatal mouse heart: a proteomic study. Radiat Environ Biophys. 2013 Jul 24.
PubMed PMID: 23880982. Epub 2013/07/25. Eng.
(PS2-22) Epigenetic effects of exposure to low doses of high-LET radiation in the mouse lung. Etienne
1
1
1
1
1
Nzabarushimana ; Isabelle R. Miousse, PhD ; Lijian Shao, PhD ; Jianhui Chang, PhD ; Antino R. Allen, PhD ;
3
2
2
2
Jennifer Turner, PhD ; Blair Stewart, PhD ; Jacob Raber, PhD ; Gregory Nelson, PhD ; and Igor Koturbash,
1
2
1
MD PhD, UAMS, Little Rock, AR ; Oregon Health and Science University, Portland, OR ; and Loma Linda
University, Loma Linda, CA
3
The long-term health effects of exposure to high-LET radiation and the underlying mechanisms
are poorly understood. Studies show that space missions can result in the development of pulmonary
56
pathological states. Our initial study demonstrated that exposure to low doses of Fe resulted in minor
pro-fibrotic changes exhibited primarily as increased expression of chemokines and interleukins, detected
at the beginning of the fibrotic phase (22 weeks post exposure). At the same time-point, epigenetic
alterations were exhibited as global DNA and repetitive elements-associated hypermethylation and
146 | P a g e
inhibits cell proliferation and induces S phase arrest via targeting cyclin A2.
(PS2-21) PPAR alpha: a key regulator of progressive metabolic changes after neonatal total body low-
1
1
1
dose ionizing radiation. Mayur V. Bakshi ; Omid Azimzadeh, PhD ; Zarko Barjaktarovic, PhD ; Stefan J.
2
1
3
3
1
Kempf ; Juliane Merl, PhD ; Sonja Buratovic ; Per Eriksson, PhD ; Micheal J. Atkinson, PhD ; and Soile
1
1
Tapio, PhD, Inst. of Radiation Biology, Helmholtz Center Munich, Neuherberg, Germany ; Research Unit
2
Protein Science, Helmholtz Center Munich, Nuherberg, Germany ; and Department of Environmental
3
Toxicology, Uppsala University, Uppsala, Sweden
Effects of low-dose total body ionizing radiation are becoming a major cause of concern for
radiation protection. Epidemiological studies have shown that children and young adults are especially
susceptible to radiation-induced cardiovascular disease (CVD). Long-term effects of low and moderate
doses of ionizing radiation target the metabolic system directly or indirectly, especially when the body
60
needs adaptation to metabolic tuning. In this study NMRI mice received single doses of total body Co
137
or Cs gamma-irradiation on postnatal day (PND) 10 and were sacrificed either at PND 11 or 7 months
post-irradiation. The doses used were 0.02/0.05, 0.10, 0.50 and 1.0 Gy. Changes in cardiac and liver
protein expression were quantified using Isotope Coded Protein Label (ICPL) and tandem mass
spectrometry (LC-MS/MS). Progressive structural and metabolic impairments were observed in both
organs. We observed decrease in pyruvate metabolism in liver and shock response (dose dependent up-
++
regulation of Ca ATPases Atp2a2) in heart as immediate responses on PND 11. Interestingly, the
transcription factor peroxisome proliferator-activated receptor (PPAR) alpha was found to be activated in
heart and deactivated in liver after 7 months. Inflammatory processes that are partly regulated by PPAR
alpha were found to be affected in both organs at all doses and time points. These observations were
proven by immuno-blotting and activity assays. PPAR alpha is an essential transcription factor involved in
metabolic adaptations in neonates, especially for lipid metabolic processes. This study highlights PPAR
alpha as the long-term key regulator of metabolic homeostasis after exposure to low and moderate dose
ionizing radiation in neonatal stage. Reference: Bakshi MV, et al. Long-term effects of acute low-dose
ionizing radiation on the neonatal mouse heart: a proteomic study. Radiat Environ Biophys. 2013 Jul 24.
PubMed PMID: 23880982. Epub 2013/07/25. Eng.
(PS2-22) Epigenetic effects of exposure to low doses of high-LET radiation in the mouse lung. Etienne
1
1
1
1
1
Nzabarushimana ; Isabelle R. Miousse, PhD ; Lijian Shao, PhD ; Jianhui Chang, PhD ; Antino R. Allen, PhD ;
3
2
2
2
Jennifer Turner, PhD ; Blair Stewart, PhD ; Jacob Raber, PhD ; Gregory Nelson, PhD ; and Igor Koturbash,
1
2
1
MD PhD, UAMS, Little Rock, AR ; Oregon Health and Science University, Portland, OR ; and Loma Linda
University, Loma Linda, CA
3
The long-term health effects of exposure to high-LET radiation and the underlying mechanisms
are poorly understood. Studies show that space missions can result in the development of pulmonary
56
pathological states. Our initial study demonstrated that exposure to low doses of Fe resulted in minor
pro-fibrotic changes exhibited primarily as increased expression of chemokines and interleukins, detected
at the beginning of the fibrotic phase (22 weeks post exposure). At the same time-point, epigenetic
alterations were exhibited as global DNA and repetitive elements-associated hypermethylation and
146 | P a g e
