John J. Mieyal

Learn More
Sulfhydryl chemistry plays a vital role in normal biology and in defense of cells against oxidants, free radicals, and electrophiles. Modification of critical cysteine residues is an important mechanism of signal transduction, and perturbation of thiol-disulfide homeostasis is an important consequence of many diseases. A prevalent form of cysteine(More)
In response to growth factor stimulation, many mammalian cells transiently generate reactive oxygen species (ROS) that lead to the elevation of tyrosine-phosphorylated and glutathionylated proteins. While investigating EGF-induced glutathionylation in A431 cells, paradoxically we found deglutathionylation of a major 42-kDa protein identified as actin. Mass(More)
Oxidative stress broadly impacts cells, initiating regulatory pathways as well as apoptosis and necrosis. A key molecular event is protein S-glutathionylation, and thioltransferase (glutaredoxin) is a specific and efficient catalyst of protein-SSG reduction. In this study 30-min exposure of H9 and Jurkat cells to cadmium inhibited intracellular protein-SSG(More)
In murine embryonic fibroblasts, N-acetyl-L-cysteine (NAC), a GSH generating agent, enhances hypoxic apoptosis by blocking the NFkappaB survival pathway (Qanungo, S., Wang, M., and Nieminen, A. L. (2004) J. Biol. Chem. 279, 50455-50464). Here, we examined sulfhydryl modifications of the p65 subunit of NFkappaB that are responsible for NFkappaB inactivation.(More)
Reversible protein S-glutathionylation (protein-SSG) is an important post-translational modification, providing protection of protein cysteines from irreversible oxidation and serving to transduce redox signals. Analogous to phosphatases, glutaredoxin (GRx) enzymes catalyze deglutathionylation of proteins, regulating diverse intracellular signaling(More)
SIGNIFICANCE Neurodegenerative diseases are characterized by progressive loss of neurons. A common feature is oxidative stress, which arises when reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) exceed amounts required for normal redox signaling. An imbalance in ROS/RNS alters functionality of cysteines and perturbs thiol-disulfide(More)
Glutaredoxin (GRx, thioltransferase) is implicated in cellular redox regulation, and it is known for specific and efficient catalysis of reduction of protein-S-S-glutathione-mixed disulfides (protein-SSG) because of its remarkably low thiol pK(a) ( approximately 3.5) and its ability to stabilize a catalytic S-glutathionyl intermediate (GRx-SSG). These(More)
Reversible posttranslational modifications on specific amino acid residues can efficiently regulate protein functions. O-Phosphorylation is the prototype and analogue to the rapidly emerging mechanism of regulation known as S-glutathionylation. The latter is being recognized as a potentially widespread form of modulation of the activities of redox-sensitive(More)
S-glutathionylation is a reversible post-translational modification that continues to gain eminence as a redox regulatory mechanism of protein activity and associated cellular functions. Many diverse cellular proteins such as transcription factors, adhesion molecules, enzymes, and cytokines are reported to undergo glutathionylation, although the functional(More)
Thioltransferase activity was identified and the enzyme purified to apparent homogeneity from human red blood cells. Activity was measured as glutathione-dependent reduction of the prototype substrate hydroxyethyl disulfide; formation of oxidized glutathione (GSSG) was coupled to NADPH oxidation by GSSG reductase (1 unit of activity = 1 mumol/min of NADPH(More)