Glutamine Synthetase, PFOS and Neurotransmission

PFC are chemicals that are ubiquitous in the environmental and can or could be found in products including building materials, fabrics, packaging, clothing, protective gear etc. Recent studies show that these chemicals have the capacity to regulate or impair gene expression including those that regulate the excretion of toxic waste products that may result in alterations of neurotransmission and contribute to their toxicity. In addition, genetic problems may aggravate this inhibition and augment the physical consequences of exposure. Glutamine synthetase is one enzyme that is important for regulation of toxins such as ammonia in the brain as well as production of glutathione. In addition, certain conditions, such as in endotoxemia and implicated as a causal factor is CFS, the activity of this enzyme is further reduced. Nrf2 is protective against PFOS through the generation of HO-1 and reductions in its production may augment oxidative stress damage from PFOS.


Yang, X., Wang, L., Sun, W., and Xue, Z. (2009). [effects of perfluorooctane sulfonate on amino acid neurotransmitters and glutamine synthetase in rats]. Wei sheng yan jiu = Journal of hygiene research, 38(1):19-21. http://www.citeulike.org/user/HEIRS/article/6999108
Häussinger, D. and Schliess, F. (2007). Glutamine metabolism and signaling in the liver. Frontiers in Bioscience, 12:371-391.
http://www.citeulike.org/user/HEIRS/article/7208003
Shi, X. and Zhou, B. (2010). The role of nrf2 and mapk pathways in pfos-induced oxidative stress in zebrafish embryos. Toxicol. Sci., 115(2):391-400.
http://www.citeulike.org/user/HEIRS/article/6761678

The specificity of neuroprotection by antioxidants.

In this model, extracellularly added glutamate inhibits cystine uptake through the cystine/glutamate antiporter, resulting in the depletion of intracellular cysteine and GSH. When the cellular GSH level drops below 20% of the control, an explosive generation of ROS occurs that is required for the subsequent cell death. (Pg. 13)

Liu, Y. and Schubert, D. (2009). The specificity of neuroprotection by antioxidants. Journal of Biomedical Science, 16(1):98+. http://www.citeulike.org/user/HEIRS/article/6079766

Hydrogen Sulfide Increases Glutathione Production and Suppresses Oxidative Stress in Mitochondria

Title: Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria.

Summary: "H2S enhances GSH by enhancing cystine/cysteine transporters and redistributes GSH to mitochondria. H2S produced in mitochondria also may directly suppress oxidative stress. It provides a new mechanism of neuroprotection from oxidative stress by H2S."

Kimura, Y., Goto, Y.-I., and Kimura, H. (2009). Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria. Antioxidants & Redox Signaling, pages 091026040507095+. http://www.citeulike.org/user/HEIRS/article/6015103