Acrolein is a highly electrophilic alpha, beta-unsaturated
aldehyde to which humans are exposed in many situations and has been implicated in
neurodegenerative diseases such as
Alzheimer's disease. A galloyl dimer prorobinetinidin from Acacia mearnsii De Wild,
robinetinidol-(4beta-->8)-
epigallocatechin 3-O-gallate (REO), has
antioxidant properties and could protect brain against
acrolein-induced oxidative damage. In this study, the molecular basis of
acrolein-induced cytotoxicity in human
neuroblastoma SH-SY5Y cells and the modulating effects of REO were examined. Our results indicate that REO protects SH-SY5Y cells from
acrolein-induced damage by the attenuation of
reactive oxygen species, the remediation of
NADPH oxidase activity, the enhancement of the
glutathione system, and the prevention of
protein oxidation/nitration and lipid peroxidation. In order to determine the effects of REO on mitochondrial events, mitochondrial membrane potentials (Delta Psim) and
caspase cascades downstream of mitochondria were assessed. REO inhibited the collapse of Delta Psi m, suggesting that REO reduces the
mitochondrial dysfunction associated with
acrolein treatment. REO also inhibited
caspase-3 activation, which can be triggered by mitochondrial malfunctions. Furthermore, REO induced a significant reduction in the level of phospho-JNK, which is known as an apoptotic mediator in
acrolein-induced neuronal cell death. Our results indicate that REO protects neurons from the deleterious effects of
acrolein via the attenuation of oxidative stress,
NADPH oxidase activity, GSH depletion,
protein oxidation/nitration, lipid peroxidation,
mitochondrial dysfunction, JNK activation, and
caspase activity. These findings suggest that REO could be potentially useful as a
protective agent for people exposed to
acrolein.