elevated global sumoylation in ubc9 transgenic mice protects their brains against focal cerebral ischemic damage提升全球sumoylation ubc9转基因老鼠可以保护他们的大脑不焦脑缺血性损伤.pdfVIP

Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage 1. 1. 2 1 3 Yang-ja Lee , Yongshan Mou , Dragan Maric , Dace Klimanis , Sungyoung Auh , John M. Hallenbeck1* 1 Stroke Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, United States of America, 2 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, United States of America, 3 Clinical Neurosciences Program (HNQ22), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, United States of America Abstract We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken b-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a le