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Modulation of mercury-induced mitochondria-dependent apoptosis by glycine in hepatocytes.
- Source :
-
Amino acids [Amino Acids] 2012 May; Vol. 42 (5), pp. 1669-83. Date of Electronic Publication: 2011 Mar 04. - Publication Year :
- 2012
-
Abstract
- Mercury (Hg) is one of the universal environmental pollutants and is responsible for various organ pathophysiology including oxidative stress-induced hepatic disorders. In the present study, we aimed to explore the protective role of glycine in Hg-induced cytotoxicity and cell death in murine hepatocytes. Exposure of mercury (20 μM), in the form HgCl2 for 1 h, significantly enhanced the ALT and ALP leakage, increased reactive oxygen species production, reduced cell viability and distorted the antioxidant status of hepatocytes. Flow cytometric analyses shows that Hg-induced apoptotic death in hepatocytes. Mechanism of this pathophysiology involves reduced mitochondrial membrane potential, variations in Bcl-2/Bad proteins, activation of caspases and cleavage of PARP protein. In addition, Hg distinctly increased NF-κB phosphorylation in association with IKKα phosphorylation and IκBα degradation. Concurrent treatment with glycine (45 mM), however, reduced Hg-induced oxidative stress, attenuated the changes in NF-κB phosphorylation and protects hepatocytes from Hg-induced apoptotic death. Hg also distinctly increased the phosphorylation of p38, JNK and ERK mitogen-activated protein kinase (MAPKs). Glycine treatment suppressed these apoptotic events, signifying its protective role in Hg-induced hepatocyte apoptosis as referred by reduction of p38, JNK and ERK MAPK signaling pathways. Results suggest that glycine can modulate Hg-induced oxidative stress and apoptosis in hepatocytes probably because of its antioxidant activity and functioning via mitochondria-dependent pathways and could be a beneficial agent in oxidative stress-mediated liver diseases.
- Subjects :
- Animals
Antioxidants metabolism
Cell Survival drug effects
JNK Mitogen-Activated Protein Kinases metabolism
Membrane Potential, Mitochondrial
Mice
NF-kappa B metabolism
Oxidative Stress drug effects
Proto-Oncogene Proteins c-bcl-2 metabolism
Reactive Oxygen Species metabolism
Signal Transduction
p38 Mitogen-Activated Protein Kinases metabolism
Apoptosis drug effects
Glycine administration & dosage
Hepatocytes drug effects
Mercury toxicity
Mitochondria drug effects
Protective Agents administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1438-2199
- Volume :
- 42
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Amino acids
- Publication Type :
- Academic Journal
- Accession number :
- 21373768
- Full Text :
- https://doi.org/10.1007/s00726-011-0869-3