title: Impairment of protein ubiquitination may cause delayed neuronal death.
abstract: The hippocampus is a brain structure specifically vulnerable to short periods of transient cerebral ischemia, and which displays delayed neuronal necrosis. Protein ubiquitination is a posttranslational modification of proteins and an important factor in heat shock response and a regulator of ATP-dependent protein degradation. Using affinity purified antibodies against ubiquitin and ubiquitin-protein conjugates we have found that the ubiquitin immunoreactivity (UIR), normally present in all neurons of the hippocampus, disappears in the early recirculation period following cerebral ischemia from all hippocampal cells except the interneurons. Later UIR reappears in the different hippocampal regions over a 72 h period in the following order: granule cells-CA3 pyramidal cells-CA2 pyramidal cells. This is the inverse order of sensitivity of these cells to ischemia. The UIR never recovers in the CA1 pyramidal neurons where a 95% neuronal necrosis is seen following three days of recovery. We propose that the loss of UIR in the pyramidal neurons in the CA1 region signifies a persistent impairment of protein ubiquitination, and thus a change in the turnover of structural and regulatory proteins, which could be an essential part of the mechanism of slow neuronal death following cerebral ischemia.
authors.affiliation: Laboratory for Experimental Brain Research, Lund Hospital, University of Lund, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Magnusson
authors.forename: T
authors.initials: T
authors.lastname: Wieloch
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D014452:Ubiquitins