Ammonia Upregulates Membrane Channel Associated with Autoimmune Conditions in Astrocytes~!

"Ammonium chloride induced upregulation of aquaporin-4 in astrocytes is regulated by the p38 mitogen-activated protein kinase pathway. Inhibiting p38 activation prevented ammonium chloride induced aquaporin-4 protein upregulation." It has been suggested that aquaporins are responsible for autoimmune-type conditions including MS and past studies show it upregulates the inflammatory cytokine that initiates the inflammatory cascade that increases oxidative stress via NO.

CiteULike: Ammonia induces upregulation of aquaporin-4 in neocortical astrocytes of rats through the p38 mitogen-activated protein kinase pathway.:


Reference: (2005). Aquaporin-4, water channel protein implicated in a disorder similar to multiple sclerosis. http://www.citeulike.org/user/HEIRS/article/7859740
Sinke, A. P., Jayakumar, A. R., Panickar, K. S., Moriyama, M., Reddy, P. V., and Norenberg, M. D. (2008). Nfkappab in the mechanism of ammonia-induced astrocyte swelling in culture. Journal of neurochemistry, 106(6):2302-2311.

CiteULike: NF-kappaB Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells.

The suggests existence of a molecular CO(2) sensor in mammalian cells that is linked to the regulation of genes involved in innate immunity and inflammation.

CiteULike: NF-kappaB Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells.: "Cummins, E. P., Oliver, K. M., Lenihan, C. R., Fitzpatrick, S. F., Bruning, U., Scholz, C. C., Slattery, C., Leonard, M. O., McLoughlin, P., and Taylor, C. T. (2010). Nf-kappab links co2 sensing to innate immunity and inflammation in mammalian cells. Journal of immunology (Baltimore, Md. : 1950)."

Resveratrol differentially modulates inflam responses of microglia & astrocytes

Comment: An extremely useful read for those interested in this kind of stuff. Full text available.

"the first report of a difference between microglial cell and astrocyte in response to LPS, and of a difference in the capacity of resveratrol to protect microglia and astrocytes from inflammatory insults."


Lu, X., Ma, L., Ruan, L., Kong, Y., Mou, H., Zhang, Z., Wang, Z., Wang, J. M., and Le, Y. (2010). Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. Journal of Neuroinflammation, 7(1):46+.  http://www.citeulike.org/user/HEIRS/article/7694580

Nair, S., Barve, A., Khor, T.-O. O., Shen, G.-X. X., Lin, W., Chan, J. Y., Cai, L., and Kong, A.-N. N. (2010). Regulation of nrf2- and ap-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of nrf2-knockout or c57bl/6j mice and pc-3 ap-1 human prostate cancer cells. Acta pharmacologica Sinica. http://www.citeulike.org/user/HEIRS/article/7694509

Food Molds: Does Impairment of PGC-1a Contribute to Their Toxicity?

Background: PGC-1a is an important regulator of metabolism in different tissues including the muscle and liver and its expression may be of important significance in a variety of diseases including neurodegenerative diseases and diabetes and influences circadian rythyms.  In addition, its activities are directly influenced by a number of other proteins including AMPK and SIRT1.

Vomitoxin, also known as deoxynivalenol (DON) is a  mycotoxin found in different types of foodstuffs and can be associated with mycotoxicosis in both animals and humans.While its negative health effects are generally milder than other mycotoxins susceptible populations could be more at risk. Generally, this class of mycotoxins are proteins inhibitors and may alter expression of neurotransmitters such as serotonin which can lead to weight loss because of the anorexic effects of elevations of serotonin.  These changes may also influence normal activity of the respiratory tract. (Wipedia) According to a recent study and in-line with the DON's ability to negative influence protein expression, DON has been demonstrated to upregulate a known of repressor of PGC-1a in addition to other proteins.  This could explain why individuals ( or animals) with impaired antioxidant and immune systems, metabolic dysfunctions, or the aged may show more health effcts upon mold exposure. 


Osman, A. M., Pennings, J. L., Blokland, M., Peijnenburg, A., and van Loveren, H. (2010). Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (don): implications for its mechanism of action. Journal of immunotoxicology, 7(3):147-156. http://www.citeulike.org/user/HEIRS/article/7607619




Leone, T. C., Lehman, J. J., Finck, B. N., Schaeffer, P. J., Wende, A. R., Boudina, S., Courtois, M., Wozniak, D. F., Sambandam, N., Bernal-Mizrachi, C., Chen, Z., Holloszy, Medeiros, D. M., Schmidt, R. E., Saffitz, J. E., Abel, E. D., Semenkovich, C. F., and Kelly, D. P. (2005). Pgc-1α deficiency causes multi-system energy metabolic derangements: Muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 3(4):e101+.  http://www.citeulike.org/user/HEIRS/article/2909101?show_msg=already_posted

Caffeic acid phenethyl ester-mediated Nrf2 activation and IkappaB kinase inhibition are involved in NFkappaB inhibitory effect: Structural analysis for NFkappaB inhibition.

CiteULike: Caffeic acid phenethyl ester-mediated Nrf2 activation and IkappaB kinase inhibition are involved in NFkappaB inhibitory effect: Structural analysis for NFkappaB inhibition.: "that CAPE inhibits TNF-alpha-dependent NFkappaB activation via direct inhibition of IKK as well as activation of Nrf2 pathway, in which the functional groups in CAPE may be involved."

Parkinsons Model Identifies Protein & Mitochondria Metabolic Dysruptions

In Parkinson's disease model, while oxygen consumption is similar to control lines, PD lines demonstrate reduced SIRT1 phosphorylation, lower PGC-1a levels and increased NF-kabbaB activation. Results suggest altered aerobic metabolism and mitochondrial respiration.

Mitochondrial Respiration and Respiration Associated Proteins in Cell Lines Created through Parkinson's Subject Mitochondrial Transfer.: "Raquel Esteves, A., Lu, J., Rodova, M., Onyango, I., Lezi, E., Dubinsky, R., Lyons, K. E., Pahwa, R., Burns, J. M., Cardoso, S. M., and Swerdlow, R. H. (2010). Mitochondrial respiration and respiration associated proteins in cell lines created through parkinson's subject mitochondrial transfer. Journal of neurochemistry."

Epstein Barr: Interesting Interactions With Inflammatory Mediators Implicated in Environmental Illness

Summary: This nuclear translocation of NF-kappaB may promote viral latency by negatively regulating BZLF1 transcriptional activity. In situations where p65 activity is limiting in comparison to BZLF1, the ability of BZLF1 to inhibit p65 transcriptional function may protect the virus from the host immune system during the lytic form of infection.


Morrison, T. E. and Kenney, S. C. (2004). Bzlf1, an epstein-barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function. Virology, 328(2):219-232. http://www.citeulike.org/user/HEIRS/article/6463038

Inflammatory mediator NF-KappaB regulates diarrhea in inflammatory bowel disease

Inflammatory mediator regulates diarrhea in inflammatory bowel disease

ScienceDaily (2009-12-30) -- Researchers have discovered that activation of NK-kappa B, an inflammatory mediator, results in diarrhea in inflammatory bowel disease (IBD). ... > read full article

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High glucose enhances lipopolysaccharide-stimulated cd14 expression in u937 mononuclear cells by increasing nuclear factor kappab and ap-1 activities.

Nareika, A., Im, Y.-B., Game, B. A., Slate, E. H., Sanders, J. J., London, S. D., Lopes-Virella, M. F., and Huang, Y. (2008). High glucose enhances lipopolysaccharide-stimulated cd14 expression in u937 mononuclear cells by increasing nuclear factor kappab and ap-1 activities. J Endocrinol, 196(1):45-55. http://www.citeulike.org/user/HEIRS/article/3207389

More on TLR4 and LPS

Youn, H. S. S., Kim, Y. S. S., Park, Z. Y. Y., Kim, S. Y. Y., Choi, N. Y. Y., Joung, S. M. M., Seo, J. A., Lim, K.-M. M., Kwak, M.-K. K., Hwang, D. H., and Lee, J. Y. Y. (2009). Sulforaphane suppresses oligomerization of tlr4 in a thiol-dependent manner. Journal of immunology (Baltimore, Md. : 1950). http://www.citeulike.org/user/HEIRS/article/6334999

Yamawaki, Y., Kimura, H., Hosoi, T., and Ozawa, K. (2009). Myd88 plays a key role in lps-induced stat3 activation in the hypothalamus. American journal of physiology. Regulatory, integrative and comparative physiology. http://www.citeulike.org/user/HEIRS/article/6334989

Chhikara, M., Wang, S., Kern, S. J., Ferreyra, G. A., Barb, J. J., Munson, P. J., and Danner, R. L. (2009). Carbon monoxide blocks lipopolysaccharide-induced gene expression by interfering with proximal tlr4 to nf-kappab signal transduction in human monocytes. PloS one, 4(12). http://www.citeulike.org/user/HEIRS/article/6334984

Dessing, M. C., Hirst, R. A., de Vos, A. F., and van der Poll, T. (2009). Role of toll-like receptors 2 and 4 in pulmonary inflammation and injury induced by pneumolysin in mice. PloS one, 4(11). http://www.citeulike.org/user/HEIRS/article/6334977

L-theanine, an amino acid in green tea, attenuated beta-amyloid-induced cognitive dysfunction and neurotoxicity: Reduction of oxidative damages and inactivation of ERK/p38 kinase and NF-kappaB pathways.

Title: L-theanine, an amino acid in green tea, attenuated beta-amyloid-induced cognitive dysfunction and neurotoxicity: Reduction of oxidative damages and inactivation of ERK/p38 kinase and NF-kappaB pathways.


Citation: Kim, T. I. I., Lee, Y. K. K., Park, S. G. G., Choi, I. S. S., Ban, J. O. O., Park, H. K. K., Nam, S.-Y. Y., Yun, Y. W. W., Han, S. B. B., Oh, K. W. W., and Hong, J. T. T. (2009). L-theanine, an amino acid in green tea, attenuated beta-amyloid-induced cognitive dysfunction and neurotoxicity: Reduction of oxidative damages and inactivation of erk/p38 kinase and nf-kappab pathways. Free radical biology & medicine.