Chemical stress induces the UPR stress response in olfactory neurons.

The results of a new study show chemical stress from environmental insults is a major and chronic activator of the unfolded protein response (UPR) in olfactory sensory neurons which includes activation of a number of genes. (Sammeta) Wipedia describes "UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum. In this scenario, the UPR has two primary aims: initially to restore normal function of the cell by halting protein translation (genetics) and activate the signaling pathways that lead to increasing the production of molecular chaperones involved in protein folding. If these objectives are not achieved within a certain time lapse or the disruption is prolonged, the UPR aims to initiate programmed cell death (apoptosis). One author states about the UPR in other tissues, "ischemia, chemical hypoxia and mitochondrial genetic disease (genetic hypoxia) can also induce this response." (Cortopassi)



Activity of Nrf2 is also involved with the response of chemical exposures on the nasal system which I have noted at length may be altered by a number of factors including hormone levels, ageing, nutrition,genetic factors, etc. As this article notes, the UPR response can become independant of odor-evokation and induce a loss of the enzyme CYP2A5 and REG3g. Notably, continuous activation of the UPR can alter signaling via the protein PERK through Nrf2. In 2003 Piras demonstrated that "CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region." In these findings, and because changes occurred in region that are analagous to neural glia which are active in neuroinflammation, future studies may show that changes in this area also induce neuroinflammatory responses without changes in Nrf2 levels. This study also noted alteraction in the abundance of the lectin called Reg3g....Several studies show this protein serves a homeotstatic function and this becomes important because the reduction of this lectin which kills gram (+) in the intestinal tract increases susceptibility to the effects of bacteria and includes changes in TLR signaling which may alter resistance to factors that lead to environmental disease in addtion to bacterial infection. The study of Reg3g is just begining and I am sure more studies will further clarify its role in nasal epithelia. From what has been observed thus far, this protein has been shown to have anti-diabetic properties and also may be regulated through a WNT pathway. Both of which, I have mentioned previously may influence autoimmunity, ammonia metabolism and other physiological effects that impact environmental illness especially in MCS and CFS.

You can read more about the Unfolded Protein Response here:


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Piras, E., Franzen, A., Fernandez, E. L., Bergstrom, U., Raffalli-Mathieu, F., Lang, M., and Brittebo, E. B. (2003). Cell-specific expression of cyp2a5 in the mouse respiratory tract: Effects of olfactory toxicants. J. Histochem. Cytochem., 51(11):1545-1555.
http://www.citeulike.org/user/HEIRS/article/6948536

Sammeta, N. and McClintock, T. S. (2010). Chemical stress induces the unfolded protein response in olfactory sensory neurons. The Journal of comparative neurology, 518(10):1825-1836.
http://www.citeulike.org/user/HEIRS/article/6873277?show_msg=already_posted

Kinnebrew, M. A., Ubeda, C., Zenewicz, L. A., Smith, N., Flavell, R. A., and Pamer, E. G. (2010). Bacterial flagellin stimulates toll-like receptor 5-dependent defense against vancomycin-resistant enterococcus infection. The Journal of infectious diseases, 201(4):534-543.
http://www.citeulike.org/user/HEIRS/article/6533280

Castellarin, M. L., Petropavlovskaia, M., Lipsett, M. A., and Rosenberg, L. (2007). The identification and sequence analysis of a new reg3gamma and reg2 in the syrian golden hamster. Biochimica et biophysica acta, 1769(9-10):579-585 http://www.ncbi.nlm.nih.gov/pubmed/17673309 .

Bluestone, J. A. and Hebrok, M. (2008). Safer, longer-lasting regulatory t cells with β-catenin. Nature Medicine, 14(2):118-119.
http://www.citeulike.org/user/HEIRS/article/2350828

Wipedia. Unfolded Protein Response. Retrieved on April 4, 2010. http://en.wikipedia.org/wiki/Unfolded_protein_response
 
Cortopassi, G., Danielson, S., Alemi, M., Zhan, S. S., Tong, W., Carelli, V., Martinuzzi, A., Manzuki, S., Majamaa, K., and Wong, A. (2006). Mitochondrial disease activates transcripts of the unfolded protein response and cell cycleand inhibits vesicular secretion and oligodendrocyte-specific transcripts. Mitochondria, 6:161-175. http://www.citeulike.org/user/HEIRS/article/6948589