Ubiquitin-mediated stress response in a rat model of brain transient ischemia/hypoxia.
Ubiquitin (Ub) is a small 76-residue protein, involved in intracellular protein degradation through a specific ATP-dependent system, which uses Ub as a tag to label proteins committed to be hydrolyzed by a specific 26 S protease. PGP-9.5 is another important component of the Ub system, i.e. a neuron-specific carboxyl-terminal hydrolase, which recycles Ub from Ub-polypeptide complexes. We have investigated the expression of Ub and PGP-9.5 in rat hippocampal neurons in an early phase of reperfusion in a model of transient global brain ischemia/hypoxia (bilateral occlusion of common carotid arteries for 10 min accompanied by mild hypoxia-15% O2-for 20 min), by means of immunohistochemical methods using light and electron microscopy. The intensity of Ub and PGP-9.5 immunoreactivity was evaluated by image analysis. We have detected a marked increase of Ub immunoreactivity (UIR) in neurons of CA1, CA2, CA3, CA4, and dentate gyrus subfields 1 hr after ischemia/hypoxia (but not after hypoxia only), statistically significant as confirmed by image analysis. Such increase in immunoreactivity in ischemic/hypoxic rats was localized essentially in the nuclei of hippocampal neurons. There were no changes in PGP-9.5 immunoreactivity. The data suggest that in the present model of rat brain ischemia/hypoxia Ub is involved in the neuronal stress response.
Gubellini
P
P
Dipartimento di Biologia Cellulare e dello Sviluppo, Università degli Studi di Roma, La Sapienza, Italy.
Bisso
G M
GM
Ciofi-Luzzatto
A
A
Fortuna
S
S
Lorenzini
P
P
Michalek
H
H
Scarsella
G
G
D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D006624:Hippocampus / Q000098:blood supply / Q000201:enzymology / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000201:enzymology / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000502:physiology*; D017966:Pyramidal Cells / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology*; D013869:Thiolester Hydrolases / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D014452:Ubiquitins / Q000502:physiology*
D009419:Nerve Tissue Proteins; D014452:Ubiquitins; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase