Inhibition of the Mitochondrial Permeability Transition by Aldehydes

Fructose has been shown to protect hepatocyte viability during hypoxia or exposure to mitochondrial electron transport inhibitors. We report here that the fructose metabolite d-glyceraldehyde (d-GA) is a good inhibitor of the mitochondrial permeability transition pore (PTP) in isolated rat liver mit...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-02, Vol.291 (2), p.215-219
Main Authors: Irwin, William A., Gaspers, Lawrence D., Thomas, John A.
Format: Article
Language:English
Subjects:
aldehyde
Aldehyde Dehydrogenase - metabolism
aldehydes
Aldehydes - pharmacology
Animals
Calcium Chloride - antagonists & inhibitors
dehydrogenase
fructose
Glyceraldehyde - pharmacology
hepatocytes
Intracellular Membranes - drug effects
Intracellular Membranes - metabolism
Ion Channels
Kinetics
Membrane Proteins - antagonists & inhibitors
Mitochondria, Liver - drug effects
Mitochondria, Liver - metabolism
Mitochondrial Membrane Transport Proteins
mitochondrial permeability transition
Permeability - drug effects
Phenylglyoxal - pharmacology
Rats
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Summary:Fructose has been shown to protect hepatocyte viability during hypoxia or exposure to mitochondrial electron transport inhibitors. We report here that the fructose metabolite d-glyceraldehyde (d-GA) is a good inhibitor of the mitochondrial permeability transition pore (PTP) in isolated rat liver mitochondria. We propose that a substantial portion of the protective effect of fructose on hepatocytes is due to d-GA inhibition of the permeability transition. Aldehydes which are substrates of the mitochondrial aldehyde dehydrogenase (mALDH) afford protection, while poor substrates do not. Protection is prevented by the ALDH inhibitor chloral hydrate. We propose that the NADH/NAD+ ratio is the key to protection. The aldehydes phenylglyoxal (PGO) and 4-hydroxynonenal (4-HNE), which have previously been shown to inhibit the PTP, apparently function by a different mechanism independent of mALDH activity. Both PGO or 4-HNE are themselves potent inhibitors of ALDH, and their protective effect cannot be blocked by an ALDH inhibitor.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2002.6457