Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer's disease hippocampus.
Recently, it has been reported that Kalirin gene transcripts are under-expressed in AD hippocampal specimens compared to the controls. The Kalirin gene generates a dozen Kalirin isoforms. Kalirin-7 is the predominant protein expressed in the adult brain and plays crucial roles in growth and maintenance of neurons. Yet its role in human diseases is unknown. We report that Kalirin-7 is significantly diminished both at the mRNA and protein levels in the hippocampus specimens from 19 AD patients compared to the specimens from 15 controls. Kalirin-7 associates with iNOS in the hippocampus, and therefore, Kalirin-7 is complexed with iNOS less in AD hippocampus extracts than in control hippocampus extracts. In cultured cells, Kalirin-7 associates with iNOS and down-regulates the enzyme activity. The down-regulation is attributed to the highly conserved 33 amino acid sequence, K(617) -H(649), of the 1,663 amino acids long Kalirin-7. Remarkably, the iNOS activity is considerably higher in the hippocampus specimens from AD patients than the specimens from 15 controls. These observations suggest that the under-expression of Kalirin-7 in AD hippocampus correlates to the elevated iNOS activity.
Youn
HyeSook
H
Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
Ji
Inhae
I
Ji
Hanlee P
HP
Markesbery
William R
WR
Ji
Tae H
TH
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D015870:Gene Expression / Q000235:genetics*; D016678:Genome / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000276:immunology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000276:immunology; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D020662:Guanine Nucleotide Exchange Factors; D012313:RNA; D052247:Nitric Oxide Synthase Type II; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases