Acute ischemia/hypoxia in rat hippocampal neurons activates nuclear ubiquitin and alters both chromatin and DNA.
We investigated early alterations in rat neurons after experimental ischemic stress. Transient ischemia was generated by bilateral occlusion of the carotids after hypoxia. Data show a relevant increase of the nuclear level of ubiquitin 2 h post-stress as evaluated by immuno-cytolocalization. Ubiquitin returns to normal levels after 6 h. The increase in ischemic/hypoxic rats was localized preferentially in nuclei of hippocampal neurons, although some augmentation was also shown essentially in dendrites. The activation of ubiquitin system is related to a defective homeostasis and might trigger different degenerative processes. With respect to this, we observed chromatin alterations by densitometric analysis. The shown extensive DNA degeneration is consistent with the occurrence of necrotic phenomena at an early stage. However the parallel internucleosomal specific DNA fragmentation, strongly suggests that apoptotic events also occur. In any case both necrosis and apoptosis are likely to occur at same time, although apoptosis is less extensive, and the two phenomena take place in different neural cells.
Risuleo
Gianfranco
G
Dipartimento di Genetica e Biologia Molecolare, Università degli Studi di Roma 'La Sapienza', Rome, Italy.
Cristofanilli
Massimiliano
M
Scarsella
Gianfranco
G
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000737:chemistry*; D053938:DNA Fragmentation; D003720:Densitometry; D006624:Hippocampus / Q000473:pathology*; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007511:Ischemia; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism*
D002843:Chromatin; D025801:Ubiquitin; D004247:DNA