Energy metabolism inhibition impairs amyloid precursor protein secretion from Alzheimer's fibroblasts.
The present study investigates the influence of aglycemia and sodium azide (a Cytochrome c Oxidase inhibitor) on sAPP secretion from skin fibroblasts derived from sporadic AD patients and control subjects. Aglycemia reduced sAPP release in the medium of both AD and control fibroblasts to a similar extent after 2 h incubation. Treatment for 2 h with increasing azide concentrations (1 microM-100 mM) under glucose deprivation did not significantly affect sAPP secretion from control fibroblasts, but was able to significantly inhibit sAPP secretion from AD fibroblasts (maximal inhibition 51%). The failure of antioxidants like glutathione (GSH) or N-acetylcysteine (NAC) to antagonize the azide effect on AD fibroblasts and lipoperoxidation data seemed to rule out the possibility that oxidative stress could mediate the sodium azide effect on sAPP release from AD fibroblasts.
Gasparini
L
L
Neurobiology Lab, Alzheimer's Disease Unit IRCCS Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
Benussi
L
L
Bianchetti
A
A
Binetti
G
G
Curti
D
D
Govoni
S
S
Moraschi
S
S
Racchi
M
M
Trabucchi
M
M
D000111:Acetylcysteine / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007003:Hypoglycemia; D015227:Lipid Peroxidation / Q000187:drug effects; D012016:Reference Values; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019810:Sodium Azide / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D019810:Sodium Azide; D005978:Glutathione; D005947:Glucose; D000111:Acetylcysteine