Cytoprotective effects of phenolic acids on methylglyoxal-induced apoptosis in Neuro-2A cells.
In the process of glycation, methylglyoxal is a reactive dicarbonyl compound physiologically generated as an intermediate of glycolysis, and is found in high levels in blood or tissue of diabetic models. Biological glycation has been commonly implicated in the development of diabetic microvascular complications of neuropathy. Increasing evidence suggests that neuronal cell cycle regulatory failure followed by apoptosis is an important mechanism in the development of diabetic neuropathy complication. Naturally occurring antioxidants, especially phenolic acids have been recommended as the major bioactive compounds to prevent chronic diseases and promote health benefits. The objective of this study was to investigate the inhibitory abilities of phenolic acids (chlorogenic acid, syringic acid and vanillic acid) on methylglyoxal-induced mouse Neuro-2A neuroblastoma (Neuro-2A) cell apoptosis in the progression of diabetic neuropathy. The data indicated that methylglyoxal induced mouse Neuro-2A neuroblastoma (Neuro-2A) cell apoptosis via alternation of mitochondria membrane potential and Bax/Bcl-2 ratio, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase. Furthermore, the results demonstrated that activation of mitogen-activated protein kinase signal pathways (JNK and p38) participated in the methylglyoxal-induced Neuro-2A cell apoptosis process. Treatment of Neuro-2A cells with phenolic acids markedly suppresses cell apoptosis induced by methylglyoxal, suggesting that phenolic acids possess cytoprotective ability in the prevention of diabetic neuropathy complication.
Huang
Shang-Ming
SM
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Chuang
Hong-Chih
HC
Wu
Chi-Hao
CH
Yen
Gow-Chin
GC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology; D019610:Cytoprotection; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011765:Pyruvaldehyde / Q000633:toxicity*; D014641:Vanillic Acid / Q000494:pharmacology
D062385:Hydroxybenzoates; D019253:Proto-Oncogene Proteins c-bcl-2; D002726:Chlorogenic Acid; D005707:Gallic Acid; D011765:Pyruvaldehyde; C001945:syringic acid; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D014641:Vanillic Acid; C017616:phenolic acid