Global SUMOylation is a molecular mechanism underlying hypothermia-induced ischemic tolerance.

Front Cell Neurosci 2014 4;8:416. Epub 2014 Dec 4.

Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, MD, USA.

The molecular mechanisms underlying hypothermic neuroprotection have yet to be fully elucidated. Herein we demonstrate that global SUMOylation, a form of post-translational modification with the Small Ubiquitin-like MOdifer, participates in the multimodal molecular induction of hypothermia-induced ischemic tolerance. Mild (32°C) to moderate (28°C) hypothermic treatment(s) during OGD (oxygen-glucose-deprivation) or ROG (restoration of oxygen/glucose) increased global SUMO-conjugation levels and protected cells (both SHSY5Y and E18 rat cortical neurons) from OGD and ROG-induced cell death. Hypothermic exposure either before or after permanent middle cerebral artery occlusion (pMCAO) surgery in wild type mice increased global SUMO-conjugation levels in the brain and in so doing protected these animals from pMCAO-induced ischemic damage. Of note, hypothermic exposure did not provide an additional increase in protection from pMCAO-induced ischemic brain damage in Ubc9 transgenic (Ubc9 Tg) mice, which overexpress the sole E2 SUMO conjugating enzyme and thereby display elevated basal levels of global SUMOylation under normothermic conditions. Such evidence suggests that increases in global SUMOylation are critical and may account for a substantial part of the observed increase in cellular tolerance to brain ischemia caused via hypothermia.

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http://dx.doi.org/10.3389/fncel.2014.00416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255597PMC
December 2014
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References

(Supplied by CrossRef)
SUMO2/3 conjugation is an endogenous neuroprotective mechanism
Datwyler et al.
J. Cereb. Blood Flow Metab. 2011
Pathobiology of ischaemic stroke: an integrated view
Dirnagl et al.
Trends Neurosci. 1999

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