Nitric oxide activity and isoenzyme expression in the senescence-accelerated mouse p8 model of Alzheimer's disease: effects of anti-amyloid antibody and antisense treatments.
Amyloid beta protein (Abeta) in Alzheimer's disease induces oxidative stress through several mechanisms, including stimulation of nitric oxide synthase (NOS) activity. We examined NOS activity and expression in the senescence-accelerated mouse P8 (SAMP8) line. The SAMP8 strain develops with aging cognitive impairments, increases in Abeta, and oxidative stress, all reversed by amyloid precursor protein antisense or Abeta antibody treatment. We found here that hippocampal NOS activity in 12-month-old SAMP8 mice was nearly double that of 2-month-old SAMP8 or CD-1 mice, but with no change in NOS isoenzyme mRNA and protein levels. Antisense or antibody treatment further increased NOS activity in aged SAMP8 mice. Antisense treatment increased inducible NOS (iNOS) mRNA levels, decreased neuronal NOS mRNA and protein levels, but did not affect endothelial NOS (eNOS) or iNOS protein or eNOS mRNA levels. These results suggest a complex relation between Abeta and NOS in the SAMP8 that is largely mediated through posttranslational mechanisms.
Ali
Abbas K
AK
Geriatric Research Education and Clinical Center, Veterans Affairs Medical Center-St Louis, MO 63106, USA.
Banks
William A
WA
Kumar
Vijaya B
VB
Shah
Gul N
GN
Lynch
Jessica L
JL
Farr
Susan A
SA
Fleegal-DeMotta
Melissa A
MA
Morley
John E
JE
D000367:Age Factors; D000544:Alzheimer Disease / Q000201:enzymology* / Q000209:etiology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D016375:Antisense Elements (Genetics) / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000201:enzymology; D007155:Immunologic Factors / Q000627:therapeutic use*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000906:Antibodies; D016375:Antisense Elements (Genetics); D007155:Immunologic Factors; D007527:Isoenzymes; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase