Program - Society of Toxicology

44 th Annual Meeting
and ToxExpo
Program Description
WEDNESDAY
#1648 3:40 EFFECTS OF ENVIRONMENTAL AIR
POLLUTANTS ON POSTNATAL LUNG
DEVELOPMENT. M. Fanucchi. School of Veterinary
Medicine, University of California, Davis, CA.
Wednesday Afternoon, March 9
1:30 PM to 4:30 PM
Room RO3
SYMPOSIUM SESSION: ROLE OF CELL-CELL AND CELL-MATRIX
INTERACTIONS IN REGULATION OF TOXICANT-MEDIATED CELL
DEATH
Chairperson(s): Ronald Tjalkens, Colorado State University, Fort Collins,
CO.
Endorsed by:
Carcinogenesis SS*
Mechanisms SS
Neurotoxicology SS
Cell-cell interactions are key for the regulation of cell survival, cell death and
cell proliferation. Thus, an understanding of the interdependency between
different tissue cellular compartments is key to elucidating mechanisms of cell
death in response to toxicants. This symposium will provide a timely update on
the molecular mechanisms of cell death and its regulation, including the role
played by cell-cell and cell-matrix interactions. This will be illustrated by three
examples of the role these pathways play in toxicant response in diverse tissues.
The first speaker will consider how hepatic Kupffer cells are implicated in
normal homeostasis and in hepatocarcinogenesis and can mediate both hepatocyte
survival or cell death, depending on the toxic insult. The second speaker
will address how gap junctional intercellular communication and cell adhesion
are interrelated processes using the example of hexachlorobenzene which
induces a down-regulation of connexins and E-cadherin in the liver of female
but not male rats. The third speaker brings an external perspective and will
discuss how the cell detects and signals damage leading to survival or cell death.
The fourth speaker will address how neuronal trophic and communication functions
are maintained by intricate coupling with associated astroglial cells with
emphasis on neurotoxicants that selectively target astroglial cells, rendering
neurons vulnerable to both physiologic and pathophysiologic stresses. The forth
speaker will also summarise the symposium by uncovering similarities and
common themes in the role of the cellular environment in determining cell fate
after toxicant insult. This symposium will be of interest both to non-experts
looking to understand this field and those with a specific interest in cell biology,
carcinogenesis, neurotoxicology, apoptosis or cell-cell communication.
#1649 1:30 ROLE OF CELL-CELL AND CELL-MATRIX
INTERACTIONS IN REGULATION OF
TOXICANT-MEDIATED CELL DEATH. R.
Roberts 1 and R. Tjalkens 2 . 1 Safety Assessment,
AstraZeneca, Alderley Park, United Kingdom and
2 Department of Environmental and Radiological Health
Sciences, Colorado State University, Fort Collins, CO.
#1650 1:40 CELL-CELL INTERACTIONS AND THEIR ROLE
IN TOXICANT-INDUCED HEPATIC CELL
DEATH. R. Roberts. Safety Assessment, AstraZeneca,
Alderley Park, United Kingdom.
#1651 2:20 MODULATION OF CELL-CELL INTERACTIONS
BY EPIGENETIC HEPATOCARCINOGENS. M.
Charbonneau, I. Plante, N. Raynal and D. G. Cyr.
INRS-Institut Armand-Frappier, Universite du Quebec,
Pointe-Claire, Montreal, QC, Canada.
#1652 3:00 THE REGULATION OF APOPTOSIS: SURVIVAL
SIGNALLING AND THE IMPORTANCE OF
CELL TO CELL COMMUNICATION. C. Dive 1,2 , J.
T. Erler 1 , I. J. Stratford 2 , D. A. Tennant 1,3 and D. R.
Tomlinson 3 . 1 Cellular and Molecular Pharmacology
Group, Cancer Research UK Paterson Institute,
Manchester, United Kingdom, 2 School of Pharmacy and
Pharmaceutical sciences, University of Manchester,
Manchester, United Kingdom and 3 School of Biological
Sciences, University of Manchester, Manchester, United
Kingdom. Sponsor: R. Roberts.
#1653 3:40 NEURO-GLIAL INTERACTIONS IN BASAL
GANGLIA DYSFUNCTION: INSIGHTS FROM
MANGANESE NEUROTOXICITY. R. Tjalkens.
Toxicology Section, Department of Environmental and
Radiological Health Sciences, Colorado State
University, Fort Collins, CO.
Wednesday Afternoon, March 9
1:30 PM to 4:30 PM
Room RO4
SYMPOSIUM SESSION: THE UBIQUITIN- PROTEASOME SYSTEM
AS A BIOLOGICAL TARGET IN TOXIC RESPONSES AND DISEASE
Chairperson(s): Richard Pollenz, University of South Florida, Tampa, FL and
Elaine M. Faustman, Institute for Risk Analysis & Risk Communication,
Seattle, WA.
Endorsed by:
Mechanisms SS
Neurotoxicology SS
The ubiquitin-proteasome system is an essential pathway involved in covalently
modifying proteins to influence their function and turnover. The cascade is initiated
by an activating enzyme (E1), that binds to the 76 amino acid ubiquitin
protein (UB). The E1 then transfers the UB to an E2 carrier protein. Following
this transfer, a UB ligase enzyme (E3) covalently links the UB to a target
protein. It is the E3, or E3/E2 complex that supplies the target specificity of the
ubiquitination event. Genome mining has identified 530 possible genes
encoding E1, E2, E3, UB and deubiquitinating enzymes (DUB). Ubiquinated
substrates are usually recognized by the 20S or 26S proteasome complexes and
destroyed, although recent studies suggest that UB or UB-like modification does
not always result in destruction. The proteasomes are huge multiprotein
complexes that can be found in both the cytoplasm and nucleus. Overall, the
proteasome accounts for 1% of a cells protein. Due to the number of gene products
required for the ubiquitin-proteasome system, it is a prime target in various
human diseases states and cancer. Defects in the system have been implicated in
neurodegenerative diseases such as Parkinsons and Alzheimers. In addition,
studies continue to suggest that that the various enzymes of the pathway may be
targets for toxicologically relevant compounds typified by arsenic, cadmium,
TCDD and ethanol. In addition, the ubiquitin-proteasome system is implicated
in the ligand mediated degradation of important transcription factors such as
p53, steroid hormone receptors and the aryl hydrocarbon receptor (AHR). Due
to these findings, the enzymes of the ubiquitin-proteasome pathway have
become important targets in toxicology screens and in drug discovery paradigms.
#1654 1:30 THE UBIQUITIN- PROTEASOME SYSTEM AS A
BIOLOGICAL TARGET IN TOXIC RESPONSES
AND DISEASE. R. S. Pollenz. Biology, University of
South Florida, Tampa, FL.
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SOT’s 44 th Annual Meeting