Page 19 - 2014 Printable Abstract Book
P. 19
glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway,
concomitant with down-regulation of mitochondrial genes, with corresponding changes in metabolic flux
through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1α, which is
induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose
response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed
systemically in mice. This highly sensitive metabolic response to low-dose radiation has important
implications in understanding and assessing the health risks of radiation exposure.
TR9. NFKB: IMPORTANCE FOR RADIATION RESPONSES
(TR901) The Importance of NF-kappa B signaling in Radiation Responses. Mohan Natarajan,
Departments of Molecular Medicine & Radiology University of Texas Health Science Center, San
Antonio, TX
When it was discovered in 1986 by Baltimore’s group, nuclear factor kappa B (NF-kB), was thought
to be an immunoglobulin enhancer-binding protein that controls kappa enhancer activity required during
B cell maturation. Soon it was realized that NF-kB is also involved in the activation of human
immunodeficiency virus type 1 promoter (1987), and later its significance was highlighted in various types
of cancers. Within the field of radiation, the first incidence that NF-kB can be induced by moderate/high
doses of gamma radiation was documented in 1991 by Kufe et al. Soon after we showed, for the first time,
that doses of ionizing radiation as low as 0.2 Gy can potentially activate this factor and that this activation
is bi-phasic. We have also shown that the activation of NF-kB by low doses of ionizing radiation involves a
reactive oxygen signaling pathway. Our group has further extended the study on NF-kB and demonstrated
for the first tme its activation in human monocytes exposed to high LET HZE particles. Since then there
have been more than 1,400 research articles published on radiation and NF-kappa B and still there are
many more questions unanswered. NF-kB is a family of proteins that includes NF-kB1 p50/p105, NF-kB2
p52/p100, c-Rel, RelA/p65 and RelB. A diverse range of stimuli can activate NF-kB. On activation, NF-kB
can regulate a wide variety of biological effects in diverse cell types and organs. Its function has been
implicated in inflammation, cell proliferation, differentiation, apoptosis, and cell survival. Though the
activation is often through the same signaling pathway, the cellular outcome is contradictory as one can
see its involvement in cell proliferation as well as in apoptosis. Selectivity of those actions is conferred by
the expression of specific NF-kB subunits, their post transcriptional modifications, combinatorial
interactions between NF-kB and other transcription factors, and the type of association with surrounding
histones. This has led to the development of many therapeutic approaches targeting the NF-kB signaling
pathway. However, despite the tremendous progress that has been made in understanding the regulation
of NF-kB, there is much that remains to be understood. In this review, we highlight both the progress that
has been made and the fundamental questions that remain unanswered after 25 years of study. This
topical review covers the importance of this multifunctional protein in radiation research and its
significance in the radiation bystander effect.
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concomitant with down-regulation of mitochondrial genes, with corresponding changes in metabolic flux
through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1α, which is
induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose
response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed
systemically in mice. This highly sensitive metabolic response to low-dose radiation has important
implications in understanding and assessing the health risks of radiation exposure.
TR9. NFKB: IMPORTANCE FOR RADIATION RESPONSES
(TR901) The Importance of NF-kappa B signaling in Radiation Responses. Mohan Natarajan,
Departments of Molecular Medicine & Radiology University of Texas Health Science Center, San
Antonio, TX
When it was discovered in 1986 by Baltimore’s group, nuclear factor kappa B (NF-kB), was thought
to be an immunoglobulin enhancer-binding protein that controls kappa enhancer activity required during
B cell maturation. Soon it was realized that NF-kB is also involved in the activation of human
immunodeficiency virus type 1 promoter (1987), and later its significance was highlighted in various types
of cancers. Within the field of radiation, the first incidence that NF-kB can be induced by moderate/high
doses of gamma radiation was documented in 1991 by Kufe et al. Soon after we showed, for the first time,
that doses of ionizing radiation as low as 0.2 Gy can potentially activate this factor and that this activation
is bi-phasic. We have also shown that the activation of NF-kB by low doses of ionizing radiation involves a
reactive oxygen signaling pathway. Our group has further extended the study on NF-kB and demonstrated
for the first tme its activation in human monocytes exposed to high LET HZE particles. Since then there
have been more than 1,400 research articles published on radiation and NF-kappa B and still there are
many more questions unanswered. NF-kB is a family of proteins that includes NF-kB1 p50/p105, NF-kB2
p52/p100, c-Rel, RelA/p65 and RelB. A diverse range of stimuli can activate NF-kB. On activation, NF-kB
can regulate a wide variety of biological effects in diverse cell types and organs. Its function has been
implicated in inflammation, cell proliferation, differentiation, apoptosis, and cell survival. Though the
activation is often through the same signaling pathway, the cellular outcome is contradictory as one can
see its involvement in cell proliferation as well as in apoptosis. Selectivity of those actions is conferred by
the expression of specific NF-kB subunits, their post transcriptional modifications, combinatorial
interactions between NF-kB and other transcription factors, and the type of association with surrounding
histones. This has led to the development of many therapeutic approaches targeting the NF-kB signaling
pathway. However, despite the tremendous progress that has been made in understanding the regulation
of NF-kB, there is much that remains to be understood. In this review, we highlight both the progress that
has been made and the fundamental questions that remain unanswered after 25 years of study. This
topical review covers the importance of this multifunctional protein in radiation research and its
significance in the radiation bystander effect.
17 | P a g e
