4-hydroxy-2-nonenal and myricetin

There is accumulating evidence that a moderate consumption of red wine has health benefits, such as the inhibition of neurodegenerative diseases. Although this is generally attributed to resveratrol, the protective mechanisms and the active substance(s) remain unclear. We examined whether and how red wine extract (RWE) and red wine flavonols quercetin and myricetin inhibited 4-hydroxynonenal (HNE)-induced apoptosis of rat pheochromocytoma PC12 cells. RWE attenuated HNE-induced PC12 cell death in a dose-dependent manner. HNE induced cleavage of poly(ADP-ribose) polymerase, which is involved in DNA repair in the nucleus, and this was inhibited by RWE treatment. Treatment with RWE also inhibited HNE-induced nuclear condensation in PC12 cells. Data of 2',7'-dichlorofluorescin diacetate showed that RWE protected against apoptosis of PC12 cells by attenuating intracellular reactive oxygen species. The cytoprotective effects on HNE-induced cell death were stronger for quercetin and myricetin than for resveratrol. HNE-induced nuclear condensation was attenuated by quercetin and myricetin. These results suggest that the neuroprotective potential of red wine is attributable to flavonols rather than to resveratrol.

Topics: Aldehydes; Animals; Antioxidants; Apoptosis; Blotting, Western; Cell Nucleus; Cell Proliferation; Cross-Linking Reagents; Dose-Response Relationship, Drug; Flavonoids; Flavonols; Microscopy, Fluorescence; Molecular Structure; PC12 Cells; Poly(ADP-ribose) Polymerases; Quercetin; Rats; Reactive Oxygen Species; Wine

We have studied the effect of several chemical modifications to low-density lipoprotein (LDL) on its intracellular fate in macrophages. Native, acetylated and oxidized 125I-LDL were supplied to cultured peritoneal macrophages and the accumulation and distribution of labelled protein was measured both during uptake and a subsequent chase period. The intracellular accumulation of macromolecular oxidized LDL protein greatly exceeded that of acetylated LDL, despite similar rates of uptake and common endocytic receptors. The accumulation of intracellular apoprotein was proportional to the extent to which the LDL was first oxidized. ApoB of oxidized LDL was more resistant to proteolysis by lysosomal enzymes than native apoB. Interestingly, acetylated apoB is more rapidly hydrolysed than the native protein. 125I-LDL modified with 4-hydroxynonenal (HNE) and myricetin, but not with malondialdehyde (MDA), was also accumulated within macrophages in a high-molecular weight fraction, and was resistant to cell-free lysosomal proteolysis. These forms of LDL also contained crosslinked apoB molecules. It is suggested that the accumulation of oxidized LDL within macrophages may he due, at least in part, to the formation of inter- or intra-molecular crosslinks in apoB which render it less accessible to proteolysis.

Topics: Aldehydes; Animals; Apolipoproteins B; Cells, Cultured; Cross-Linking Reagents; Electrophoresis, Polyacrylamide Gel; Endocytosis; Flavonoids; Humans; Hydrolysis; Lipoproteins, LDL; Macrophages; Malondialdehyde; Mice; Oxidation-Reduction