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Cadmium Induced Oxidative Stress and Glutathionylation
Author(s) -
Ouellette Steven B.,
Stapleton Susan R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a528-b
Subject(s) - glutathione , reactive oxygen species , oxidative stress , chemistry , biochemistry , lipid peroxidation , superoxide dismutase , superoxide , mitochondrial ros , microbiology and biotechnology , biology , enzyme
Oxidative stress is the result of a cellular imbalance of pro‐oxidants and anti‐oxidants, with the pro‐oxidants being in much higher concentration. This imbalance has been shown to result in disease due to cellular damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Pro‐oxidants such as ROS are generated upon exposure to heavy metals, including cadmium (Cd). Cd has become a problematic pollutant due to the industrial production and eventual deposition of batteries and plastics. Cd has also been shown to elevate ROS in a rat hepatocyte model and as a result induce lipid peroxidation, chromosomal damage and LDH leakage. Cd exposure also results in a decrease of reduced glutathione. Glutathione, a ubiquitous tripeptide, serves as an indicator of the redox state of the cell, but also has a protective role in guarding proteins against permanent damage by ROS. This protective role is exemplified in particular with active site Cys residues. Glutathione can bind these residues in a reversible manner, forming a glutathionylated protein (GSSP) when the cell is under attack by ROS, avoiding an irreversible modification that occurs when oxygen radicals such as superoxide and hydrogen peroxide react with the residue. In this study, the effects of Cd induced oxidative stress on the rat hepatoma cell line H4IIE are considered. Western blot analysis is used to probe for the presence of GSSPs. The results indicate that the presence of GSSPs vary with exposure time of Cd. Based on molecular weight comparison of the GSSPs, possible candidates for the proteins that are being modified by GSH include those from the SAPK cascade, which include p38, ERK and JNK. Work is continuing to identify the protein(s) that are glutathionylated, and their role in self‐preservation used by the cell to survive cadmium exposure. This work was supported in part by NSF 0136127.