title: HuR function and translational state analysis following global brain ischemia and reperfusion.
abstract: Prolonged translation arrest in post-ischemic hippocampal CA1 pyramidal neurons precludes translation of induced stress genes and directly correlates with cell death. We evaluated the regulation of mRNAs containing adenine- and uridine-rich elements (ARE) by assessing HuR protein and hsp70 mRNA nuclear translocation, HuR polysome binding, and translation state analysis of CA1 and CA3 at 8 h of reperfusion after 10 min of global cerebral ischemia. There was no difference between CA1 and CA3 at 8 h of reperfusion in nuclear or cytoplasmic HuR protein or hsp70 mRNA, or HuR polysome association, suggesting that neither mechanism contributed to post-ischemic outcome. Translation state analysis revealed that 28 and 58 % of unique mRNAs significantly different between 8hR and NIC, in CA3 and CA1, respectively, were not polysome-bound. There was significantly greater diversity of polysome-bound mRNAs in reperfused CA3 compared to CA1, and in both regions, ARE-containing mRNAs accounted for 4-5 % of the total. These data indicate that posttranscriptional ARE-containing mRNA regulation occurs in reperfused neurons and contributes to post-ischemic outcome. Understanding the differential responses of vulnerable and resistant neurons to ischemia will contribute to the development of effective neuroprotective therapies.
authors: Department of Physiology, Wayne State University School of Medicine, 4116 Scott Hall, 540 East Canfield Ave, Detroit, MI, 48201, USA.
authors: Jeffrey J
authors: JJ
authors: Szymanski
authors: Haihui
authors: H
authors: Wang
authors: Jill T
authors: JT
authors: Jamison
authors: Donald J
authors: DJ
authors: DeGracia
mesh_terms: D000225:Adenine / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D056654:CA3 Region, Hippocampal / Q000378:metabolism*; D051959:ELAV Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism
chemical_list: D051959:ELAV Proteins; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D000225:Adenine; D014529:Uridine