Search PubMed⌕ Search

Biomedical subjects

M Guichardant

Publications and source records attributed to M Guichardant.

43 records · Page 3Linked to original sources

Aldehydes from n-6 fatty acid peroxidation. Effects on aminophospholipids.

4-Hydroxy-nonenal (4-HNE) is a major by-product of n-6 fatty acid peroxidation. It has been described to covalently bind biomolecules expressing primary amine, especially the Lys residues in proteins. Low-density lipoproteins (LDL) are well-described macromolecules to be modified by 4-HNE, making them available to scavenger receptors on macrophages. Those macrophages then become foam cells and play an active role in atherogenesis. This paper reports on the covalent binding of 4-HNE to phosphatidylethanolamine (PE), a major aminophospholipid in biological membranes. In contrast, phosphatidylserine (PS) is virtually not modified by 4-HNE. One stable adduct, the Michael adduct PE/4-HNE is a poor substrate of secreted phospholipase A(2) and is not cleaved by phospholipase D. Plasmalogen PE, an important subclass of PE, is covalently modified by 4-HNE as well, but appears to be further degraded on its sn-1 position, the alkenyl chain, which might alter the antioxidant potential of the molecule. An aldehyde homologous to 4-HNE has been characterized as a breakdown product of 12-hydroperoxyeicosatetraenoic acid (12-HpETE) and named 4-hydroxy-2E,6Z-dodecadienal (4-HDDE). This compound as well as 4-HNE was detected in human plasma. Finally, 4-HDDE appears almost 3-fold more active than 4-HNE to make covalent adducts with PE. We conclude that 4-HNE and 4-HDDE are two biologically relevant markers of n-6 fatty acid peroxidation that may alter the phospholipid-dependent cell signaling.

Aldehydes↗

Mitochondrial H2O2 production is reduced with acute and chronic eccentric exercise in rat skeletal muscle.

Oxidative stress with acute/chronic exercise has been so far examined using exercise involving a combination of concentric and eccentric contractions, but skeletal muscles are likely to be injured to a greater extent by pliometric contractions. In the present study, the effects of acute and chronic bouts of downhill running exercise on mitochondrial hydrogen peroxide (H2O2) generation (fluorimetric detection of a dimer with homovanillic acid in presence of horseradish peroxidase) and oxygen consumption in conjunction with antioxidant enzymes activity were examined. The results show that acute eccentric exercise was accompanied by a significantly reduced mitochondrial H2O2 production that is likely due to a decrease in complex I of the electron transport chain (ETC). On the other hand, eccentric training leads to positive adaptations, reflected by a higher citrate synthase activity and decreased mitochondrial H2O2 production. The decrease in mitochondrial H2O2 cannot be attributed to alterations in antioxidant capacities but rather to changes in mitochondrial membrane composition characterized by an increased polyunsaturated to saturated fatty acids ratio, and decreased contents in arachidonic acid and plasmalogens. These results suggest that changes in mitochondrial membrane properties with eccentric training can affect H2O2 production by muscle mitochondria. It is hypothesized that these changes resulted in a mild uncoupling sufficient to reduce electron back flow through complex I of the ETC, the major generator of reactive oxygen species by skeletal muscle mitochondria.

Animals↗