title: Iron induces hepatocytes death via MAPK activation and mitochondria-dependent apoptotic pathway: beneficial role of glycine.
abstract: In the present study we investigated the beneficial role of glycine in iron (FeSO₄) induced oxidative damage in murine hepatocytes. Exposure of hepatocytes to 20 μM FeSO₄ for 3 hours enhanced reactive oxygen species (ROS) generation and induced alteration in biochemical parameters related to hepatic oxidative stress. Investigating cell signalling pathway, we observed that iron (FeSO₄) intoxication caused NF-κB activation as well as the phosphorylation of p38 and ERK MAPKs. Iron (FeSO₄) administration also disrupted Bcl-2/Bad protein balance, reduced mitochondrial membrane potential, released cytochrome c and induced the activation of caspases and cleavage of PARP protein. Flow cytometric analysis also confirmed that iron (FeSO₄) induced hepatocytes death is apoptotic in nature. Glycine (10 mM) supplementation, on the other hand, reduced all the iron (FeSO₄) induced apoptotic indices. Combining, results suggest that glycine could be a beneficial agent against iron mediated toxicity in hepatocytes.
authors: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors: Sudip
authors: S
authors: Bhattacharyya
authors: Jyotirmoy
authors: J
authors: Ghosh
authors: Parames C
authors: PC
authors: Sil
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation; D005290:Ferric Compounds / Q000633:toxicity*; D005998:Glycine / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C024823:ferric sulfate; D020928:Mitogen-Activated Protein Kinases; D005998:Glycine