global protein conjugation by ubiquitin-like-modifiers during ischemic stress is regulated by micrornas and confers robust tolerance to ischemia全球蛋白质结合ubiquitin-like-modifiers在缺血性压力是由小分子核糖核酸和缺血带来强劲的宽容.pdfVIP

Global Protein Conjugation by Ubiquitin-Like-Modifiers during Ischemic Stress Is Regulated by MicroRNAs and Confers Robust Tolerance to Ischemia 1 2 1 Yang-ja Lee , Kory R. Johnson , John M. Hallenbeck * 1 Stroke Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, United States of America, 2 Bioinformatics Section, Information Technology Bioinformatics Program, Division of Intramural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, United States of America Abstract Hibernation torpor provides an excellent model of natural tolerance to ischemia. We have previously shown that massive global SUMOylation occurs during hibernation torpor in ground squirrels. We have also shown that overexpression of Ubc9, SUMO-1, or SUMO-2/3 provides protection against ischemic damage in cell lines and cortical neurons exposed to oxygen/ glucose deprivation, and in mice exposed to middle cerebral artery occlusion. We have now extended our study to other Ubiquitin-Like- Modifiers (ULMs), which have multiple cellular functions during stress, in order to assess the possibility that they also have roles in tolerance to ischemia. We found that not only SUMO conjugation, but also global protein conjugation by other ULMs including NEDD8, ISG15, UFM1 and FUB1 were significantly increased in the brains of hibernating ground squirrels during torpor. By means of miRNA microarrays of ground squirrel brain samples (from active and torpor phase) we found that the miR-200 family (miR-200a,b,c/miR-141/miR-429) and the miR-182 family (miR-182/miR- 183/miR-96) were among the most consistently d