Protective effects of methyl gallate on H2O2-induced apoptosis in PC12 cells.
Neurodegenerative disorders are a class of diseases that have been linked to apoptosis induced by elevated levels of reactive oxygen species (ROS). ROS activates the apoptotic cascade through mitochondrial dysfunction and damage to lipids, proteins and DNA. Recently, fruit and tea-derived polyphenols have been found to be beneficial in decreasing oxidative stress and increasing overall health. Further, polyphenols including epigallocatechin gallate (EGCG) have been reported to inhibit apoptotic signaling and increase neural cell survival. In an effort to better understand the beneficial properties associated with polyphenol consumption, the aim of this study was to explore the neuroprotective effects of EGCG, methyl gallate (MG), gallic acid (GA) and N-acetylcysteine (NAC) on H(2)O(2)-induced apoptosis in PC12 cells and elucidate potential protective mechanisms. Cell viability data demonstrates that MG and NAC pre-treatments significantly increase viability of H(2)O(2)-stressed cells, while pre-treatments with EGCG and GA exacerbates stress. Quantitation of apoptosis and mitochondrial membrane potential shows that MG pre-treatment prevents mitochondria depolarization, however does not inhibit apoptosis and is thus evidence that MG can inhibit mitochondria-mediated apoptosis. Subsequent analysis of DNA degradation and caspase activation reveals that MG inhibits activation of caspase 9 and has a partial inhibitory effect on DNA degradation. These findings confirm the involvement of both intrinsic and extrinsic apoptotic pathways in H(2)O(2)-induced apoptosis and suggest that MG may have potential therapeutic properties against mitochondria-mediated apoptosis.
Crispo
James A G
JA
Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON, Canada.
Piché
Matthew
M
Ansell
Dominique R
DR
Eibl
Joseph K
JK
Tai
Isabella T
IT
Kumar
Aseem
A
Ross
Gregory M
GM
Tai
T C
TC
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D000975:Antioxidants; D018696:Neuroprotective Agents; C052082:methyl gallate; D005707:Gallic Acid; D006861:Hydrogen Peroxide; D000111:Acetylcysteine