Format

Send to

Choose Destination
Biochem Biophys Res Commun. 1999 Apr 13;257(2):440-7.

Glucose protection from MPP+-induced apoptosis depends on mitochondrial membrane potential and ATP synthase.

Author information

1
Department of Neurology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York, 10029-6574, USA.

Abstract

MPP+ inhibits mitochondrial complex I and alpha-ketoglutarate dehydrogenase causing necrosis or apoptosis of catecholaminergic neurons. Low glucose levels or glycolytic blockade has been shown to potentiate MPP+ toxicity. We found that MPP+ caused concentration-dependent apoptosis of neuronally differentiated PC12 cells and that glucose, but not pyruvate, supplementation reduced apoptosis. Oligomycin concentrations sufficient to inhibit ATP synthase blocked the decreased apoptosis afforded by glucose supplementation. Laser-scanning confocal microscope imaging of chloromethyl-tetramethylrosamine methyl ester fluorescence to estimate DeltaPsiM showed that MPP+ and atractyloside reduced DeltaPsiM, while cyclosporin A (CSA) and glucose supplementation reversed decreases in DeltaPsiM caused by MPP+. Oligomycin blocked the effect of glucose supplementation on DeltaPsiM. These findings show that (i) MPP+-induced and atractyloside-induced apoptosis are associated with reduced DeltaPsiM; (ii) CSA maintains DeltaPsiM and reduces MPP+-induced apoptosis; and (iii) glucose supplementation maintains DeltaPsiM, likely by glycolytic ATP-dependent proton pumping at ATP synthase and reduces MPP+-induced apoptosis.

PMID:
10198232
DOI:
10.1006/bbrc.1999.0487
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center