Basic HTML Version
Poster Full Abstracts - Physiology and Aging
Poster board number is above title. The first author is the presenter
331
signaling pathways. A comprehensive molecular description of Nrf2 regulation is necessary to understand the function of Nrf2 as an effector of different
environmental and physiological signals and as a mediator of oxidative stress tolerance and longevity. Nrf2 binds to antioxidant response elements (AREs)
in DNA of different antioxidant and detoxification genes. The key components of the Nrf2 signaling are conserved between
Drosophila
and mammals and
CncC is the homolog of Nrf2 in flies. In order to study CncC activity in Drosophila and in cell culture, complementary
in vivo
and cell-based reporters that
carry reporter transgenes in which GFP, RFP or luciferase are regulated by synthetic ARE promoter elements, were generated. These reporters are specific to
CncC signaling and are responsive to genetic and chemical activators of Nrf2. A kinome-wide dsRNA library screen in S2 cells with the cell-based reporter
identified several novel regulators of CncC signaling. The putative regulators were validated in Drosophila using the
in vivo
reporters and were further
characterized. This study advances our understanding of the mechanism and consequences of environmental and physiological regulation of Nrf2.
748A
Transcriptional down regulation of two nuclear genes with
Frag1
and
Protein Kinase
motifs confers oxidative stress resistance and extends lifespan.
Atanu Duttaroy, Dondra Bailley, Sanjay Nag. Dept Biol, Howard Univ, Washington, DC.
Reactive Oxygen Species (ROS) poses many threats to an organism. In addition to the threats triggered by oxidative stress, ROS action is biphasic because
at low levels mitochondrial ROS intermediates many cellular signaling pathways essential to variety of biological processes. Thus ROS is already tied up
with the regulation of growth factor receptors, src kinase, ras signaling, mitogen-activated protein kinases, etc. In Drosophila, the Jun N-terminal kinase
(JNK) signal transduction pathway was identified as one of the main systems with which the fruit fly protects itself against ROS induced oxidative insults.
More recently, mitochondria and choloroplast have been identified and shown to exert their influence on nuclear gene transcription activity through a
process called retrograde signaling. The loss of function mutants of mitochondrial
Sod2
gene in Drosophila
Sod2n283
, demonstrably produces high flux of
mitochondrial superoxides. We asked if this high mitochondrial superoxide environment in
Sod2n283
is capable of activating some novel cell-signaling
pathway? Microarray analysis of
Sod2n283
followed by RNAi mediated suppression of the induced transcriptomes helped us to identify two genes,
CG4945
,
is a Serine/Threonine Protein Kinase and
CG7990
is homologous to mammalian Frag1 (FGF receptor activator) superfamily gene. While both
CG4945
and
CG7990
are upregulated more than two folds in
Sod2n283
, their RNAi mediated suppression renders the flies as highly resistant to paraquat induced
oxidative stress. Such high paraquat resistance led us to measure the lifespans of
CG4945IR
and
CG7990IR
following ubiquitous activation of the RNAi
with
Tub-GAL4
driver. Reduced
CG4945
and
CG7990
expression helps the animals to live longer, so they have an extended life span compared to the
controls. Our results demonstrate that expression of CG7990 and CG4945 are negatively required against oxidative stress protection as well for achieving
normal life span very much like the JNK, although unlike JNK these two genes are not essential for the survival of the organism.
749B
Nitric oxide signals developmental delay during regeneration.
Jacob Jaszczak, Adrian Halme. Department of Cell Biology, University of Virginia School
of Medicine, Charlottesville, VA.
In many organisms the capacity to regenerate is closely linked to development.
Drosophila
larvae are capable of robust regenerative growth within
damaged imaginal discs during larval stages. However, regeneration of damaged imaginal discs is restricted near the end of the last larval instar. We have
previously demonstrated that damage to the imaginal tissues activates a developmental checkpoint, producing a delay in development and extending the
period of regenerative competence. We have shown that the TNF-JNK pathway is necessary for producing this delay during regenerative growth, however
the systemic signals that coordinate local tissue repair with developmental progression are still unknown. Nitric oxide has been shown to be an important
signal in producing systemic responses to hypoxia or infection. Here we demonstrate that nitric oxide synthase (NOS) transcription is activated in third instar
larvae by damage to the imaginal tissues. We observe that expression of NOS protein is increased in circulating hemocytes after irradiation or targeted
imaginal disc damage, and this correlates with an increase in nitric oxide levels across the whole larva. Finally, we demonstrate that the induction of NOS
expression is sufficient to produce developmental delay, but only during a specific responsive period in the third larval instar. Based on these observations,
we propose that nitric oxide is an important regulator of developmental delay following imaginal tissue damage.
750C
Potential role of V-ATPases in autophagy regulation.
Caroline C Mauvezin, Thomas Neufeld. Department of Genetics, Cell Biology and Development,
University of Minnesota, Minneapolis, MN.
Macroautophagy (here after named autophagy) is a degradative process essential for cell survival. Indeed, autophagy is involved, for example, in the
degradation of large unhealthy organelles such as damaged mitochondria. The recent increase in awareness and interest in this field stems from the discovery
of the genes that control autophagy - the ATG genes - and the subsequent finding that autophagy can play either harmful or beneficial roles in a wide range
of areas important to human health, including cancer, neurodegeneration and aging. The core autophagic machinery is conserved from yeast to human.
Autophagy is activated by scarcity of nutrients through TOR signaling. In autophagy, double-membrane autophagosomes envelop and sequester intracellular
components and then fuse with lysosomes to form autolysosomes, which degrade their contents to regenerate nutrients. In the laboratory, we are taking
advantages of the powerful genetics of Drosophila melanogaster as a model of study to characterize the mechanisms underlying autophagic regulation.
Recently, it has been described that reactivation of TOR in mammals is autophagy-dependent and requires the degradation of autolysosomal products.
Lysosomal acidification is necessary for the proper degradation of autophagic cargo, fusion with autophagosomes and this process is directly linked with the
assemblage and the well-functioning of V-ATPase proton pump. V-ATPases are formed by two subunits V0 and V1 that are required to assemble at the
membrane of the acidic vacuoles. Each of the subunit is composed by several proteins that together form a functional complex. Interestingly, the role of V-
ATPase in membrane dynamics required for the uptake of autophagic cargo is far from fully understood and it is unknown whether V-ATPases assembly or
function is regulated by nutrients-TOR signaling. Here, we propose to target V-ATPase subunits as new regulators of autophagy. By using RNAi lines, we
propose to investigate potential variations of autophagosome induction and blockade of the autophagic flux in fat bodies of fruit flies larvae.
751A
Drosophila
, an
in vivo
model to evaluate reprotoxic damage.
PATRICIA RAMOS
1,2
, BLANCA HERNANDEZ
2
, OLGA RAMIREZ
1
. 1) Lab Genética y
Toxicología Ambiental, Depto. Biología, Facultad de Ciencias, CU, Universidad Nacional Autónoma de México, D.F., Coyoacan; 2) Drosophila Stock