Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene.
Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.
Ghidoni
R
R
Scientific Institute IRCCS Centro San Giovanni di Dio-Fatebenefratelli, Italy.
Gasparini
L
L
Alberici
A
A
Benussi
L
L
Barbiero
L
L
Mazzoli
F
F
Nicosia
F
F
Finazzi
D
D
Benerini Gatta
L
L
Albertini
A
A
Zanetti
O
O
Binetti
G
G
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D053766:Presenilin-2; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D012333:RNA, Messenger; D014157:Transcription Factors; D019810:Sodium Azide