Home
Resources
Publications
Trans-4-oxo-2-nonenal Potently Alters Mitochondrial Function

Trans-4-oxo-2-nonenal Potently Alters Mitochondrial Function

Matthew J Picklo, Alexander Azenkeng, Mark R Hoffmann

Free Radic Biol Med. 2011 Jan 15;50(2):400-7.

PMID: 21092757

Abstract:

Alzheimer disease elevates lipid peroxidation in the brain and data indicate that the resulting lipid-aldehydes are pathological effectors of lipid peroxidation. The disposition of 4-substituted nonenals derived from arachidonate (20:4, n-6) and linoleate (18:2, n-6) oxidation is modulated by their protein adduction targets, their metabolism, and the nature of the 4-substitutent. Trans-4-oxo-2-nonenal (4-ONE) has a higher toxicity in some systems than the more commonly studied trans-4-hydroxy-2-nonenal (HNE). In this work, we performed a structure-function analysis of 4-hydroxy/oxoalkenal upon mitochondrial endpoints. We tested the hypotheses that 4-ONE, owing to a highly reactive nature, is more toxic than HNE and that HNE toxicity is enantioselective. We chose to study freshly isolated brain mitochondria because of the role of mitochondrial dysfunction in neurodegenerative disorders. Whereas there was little effect related to HNE chirality, our data indicate that in the mitochondrial environment, the order of toxic potency under most conditions was 4-ONE>HNE. 4-ONE uncoupled mitochondrial respiration at a concentration of 5μM and inhibited aldehyde dehydrogenase 2 (ALDH2) activity with an IC(50) of approximately 0.5μM. The efficacy of altering mitochondrial endpoints was ALDH2 inhibition>respiration=mitochondrial swelling=ALDH5A inhibition>GSH depletion. Thiol-based alkenal scavengers, but not amine-based scavengers, were effective in blocking the effects of 4-ONE upon respiration. Quantum mechanical calculations provided insights into the basis for the elevated reactivity of 4-ONE>HNE. Our data demonstrate that 4-ONE is a potent effector of lipid peroxidation in the mitochondrial environment.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP18869302	trans-4,4′-Dibromostilbene		18869-30-2	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: