Status of the "protein kinase CK2-HMG14" system in age-related amnesia in rats.
The experiments described here demonstrate that disruption of the phosphorylation of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class may be the cause of decreased gene expression in age-related cognitive deficits. Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24 months old) was accompanied by decreases in the synthesis of synaptosomal proteins and transcription in nuclei isolated from cortical, hippocampal, and striatal neurons. There was a decrease in chromatin protein kinase CK2 activity and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2. Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5-methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14 phosphorylation by protein kinase CK2, increased transcription, increased the synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged rats. Thus, activation of the "protein kinase CK2-HMG14" system is accompanied by optimization of synaptic plasticity in aged animals. The results provide evidence for the high therapeutic potential of protein kinase CK2 activators.
Reikhardt
B A
BA
Science Research Institute of Experimental Medicine, Russian Academy of Medical Sciences, 12 Academician Pavlov Street, 197376 St. Petersburg, Russia.
Kulikova
O G
OG
Borisova
G Yu
GY
Aleksandrova
I Ya
IY
Sapronov
N S
NS
D000375:Aging / Q000502:physiology*; D000647:Amnesia / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D047388:Casein Kinases; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005042:Etimizol / Q000031:analogs & derivatives* / Q000494:pharmacology; D024241:HMGN1 Protein / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D012153:Retention, Psychology / Q000187:drug effects; D013574:Synaptosomes / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014316:Tritium / Q000378:metabolism; D014542:Uridine Monophosphate / Q000378:metabolism
D004268:DNA-Binding Proteins; D024241:HMGN1 Protein; D014316:Tritium; C040923:desmethyletimizol; D014542:Uridine Monophosphate; D011494:Protein Kinases; D047388:Casein Kinases; C093428:protein kinase CK42; D007930:Leucine; D005042:Etimizol