Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.
Abstract
<h4>Background and purpose</h4>Small ubiquitin-like modifier (SUMO) conjugation is
a post-translational modification associated with many human diseases. Characterization
of the SUMO-modified proteome is pivotal to define the mechanistic link between SUMO
conjugation and such diseases. This is particularly evident for SUMO2/3 conjugation,
which is massively activated after brain ischemia/stroke, and is believed to be a
protective response. The purpose of this study was to perform a comprehensive analysis
of the SUMO3-modified proteome regulated by brain ischemia using a novel SUMO transgenic
mouse.<h4>Methods</h4>To enable SUMO proteomics analysis in vivo, we generated transgenic
mice conditionally expressing tagged SUMO1-3 paralogues. Transgenic mice were subjected
to 10 minutes forebrain ischemia and 1 hour of reperfusion. SUMO3-conjugated proteins
were enriched by anti-FLAG affinity purification and analyzed by liquid chromatography-tandem
mass spectrometry.<h4>Results</h4>Characterization of SUMO transgenic mice demonstrated
that all 3 tagged SUMO paralogues were functionally active, and expression of exogenous
SUMOs did not modify the endogenous SUMOylation machinery. Proteomics analysis identified
112 putative SUMO3 substrates of which 91 candidates were more abundant in the ischemia
group than the sham group. Data analysis revealed processes/pathways with putative
neuroprotective functions, including glucocorticoid receptor signaling, RNA processing,
and SUMOylation-dependent ubiquitin conjugation.<h4>Conclusions</h4>The identified
proteins/pathways modulated by SUMOylation could be the key to understand the mechanisms
linking SUMOylation to neuroprotection, and thus provide new promising targets for
therapeutic interventions. The new transgenic mouse will be an invaluable platform
for analyzing the SUMO-modified proteome in models of human disorders and thereby
help to mechanistically link SUMOylation to the pathological processes.
Type
Journal articleSubject
AnimalsMice, Transgenic
Mice
Brain Ischemia
Ischemic Attack, Transient
Proteome
Ubiquitins
Small Ubiquitin-Related Modifier Proteins
SUMO-1 Protein
Proteomics
RNA Processing, Post-Transcriptional
Mass Spectrometry
Stroke
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https://hdl.handle.net/10161/23276Published Version (Please cite this version)
10.1161/strokeaha.113.004315Publication Info
(2014). Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel
small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.
Stroke, 45(4). pp. 1115-1122. 10.1161/strokeaha.113.004315. Retrieved from https://hdl.handle.net/10161/23276.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Martin Arthur Moseley III
Adjunct Professor in the Department of Cell Biology
Wulf Paschen
Professor in Anesthesiology
My research interests are understanding the mechanisms underlying induction of cell
death induced by a severe form of cellular stress. I am particularly interested in
the role of the endoplasmic reticulum in the pathological process induced by transient
cerebral ischemia and culminating in neuronal cell death. This pathological process
is associated with an irreversible suppression of protein synthese that limits the
ability of cells to withstand ischemia-induced impairment of endoplasmic r
Huaxin Sheng
Associate Professor in Anesthesiology
We have successfully developed various rodent models of brain and spinal cord injuries
in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma,
subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression
injury. We also established cardiac arrest and hemorrhagic shock models for studying
multiple organ dysfunction. Our current studies focus on two projects. One is to
examine the efficacy of catalytic antioxidant in treating cerebral is
J. Will Thompson
Adjunct Assistant Professor in the Department of Pharmacology & Cancer Biology
Dr. Thompson's research focuses on the development and deployment of proteomics and
metabolomics mass spectrometry techniques for the analysis of biological systems.
He served as the Assistant Director of the Proteomics and Metabolomics Shared Resource
in the Duke School of Medicine from 2007-2021. He currently maintains collaborations
in metabolomics and proteomics research at Duke, and develops new tools for chemical
analysis as a Princi
Wei Yang
Associate Professor in Anesthesiology
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