Modulation of mercury-induced mitochondria-dependent apoptosis by glycine in hepatocytes |
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Authors: | Pabitra Bikash Pal Sankhadeep Pal Joydeep Das Parames C Sil |
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Institution: | (1) Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054, West Bengal, India; |
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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. |
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