Proteins in Bone Health, Development and Disease in Environmental Illness

Proteins in Bone Health, Development and Disease in Environmental Illness

Flaxseed Oil May Protect Against Lead Toxicity~!

"flaxseed oil is a natural product can be protect against lead acetate-mediated hepatic cytotoxicity

Read abstract: CiteULike: The Redox Status in Rats Treated with Flaxseed Oil and Lead-Induced Hepatotoxicity.:."

Air pollution and circulating biomarkers of oxidative stress

"Chemical components of air pollutant exposures that induce oxidative stress and subsequent inflammation may be partly responsible for associations of cardiovascular morbidity and mortality with airborne particulate matter and combustion-related pollutant gasses"

Read more: CiteULike: Air pollution and circulating biomarkers of oxidative stress:

Characterization of Developmental neurotoxicity of As, Cd and Pb mixture: Synergistic Action of Metal Mixture in Glial and Neuronal Functions — Toxicol Sci

: "together, these observations are the first to show that mixture of As, Cd and Pb has the capacity to induce synergistic toxicity in astrocytes that may compromise the BBB, and may cause behaviroal dysfunction in developing rats."


Read more: Characterization of Developmental neurotoxicity of As, Cd and Pb mixture: Synergistic Action of Metal Mixture in Glial and Neuronal Functions — Toxicol Sci

Iron species mediated dopamine oxidation, proteasome inhibition and dopaminergic cell demise, implications to iron related dopaminergic neuron degeneration.

"Zhou, Z. D. D., Lan, Y. H. H., Tan, E. K. K., and Lim, T. M. M. (2010). Iron species mediated dopamine oxidation, proteasome inhibition and dopaminergic cell demise, implications to iron related dopaminergic neuron degeneration. Free radical biology & medicine."

CiteULike: Iron species mediated dopamine oxidation, proteasome inhibition and dopaminergic cell demise, implications to iron related dopaminergic neuron degeneration.:

Metals, oxidative stress and neurodegenerative disorders.

"Jomova, K., Vondrakova, D., Lawson, M., and Valko, M. (2010). Metals, oxidative stress and neurodegenerative disorders. Molecular and cellular biochemistry."

Abstract link: CiteULike: Metals, oxidative stress and neurodegenerative disorders.:

Study Says Lean Neurotoxicity Not Generated By Nitric Oxide But Gene Expression Changes~! Interesting.....

Background: Heavy metals are ubiquitous in the environment and especially found in particulate matter, jewelry and in dust especially in older homes.

In this study the expression patterns of nitric oxide synthases at the mRNA and protein levels, however, were not significantly altered by treatment with 10 mg/kg Pb. These findings indicate that Pb-induced neurotoxicity may be modulated in part by the expression of Ddah1, Sod1, Ccs, and Sfn in the olfactory bulb.

CiteULike: Effects of Lead Exposure on Nitric Oxide-associated Gene Expression in the Olfactory Bulb of Mice.: "Kim, S., Hyun, J., Kim, H., Kim, Y., Kim, E., Jang, J., and Kim, K. (2010). Effects of lead exposure on nitric oxide-associated gene expression in the olfactory bulb of mice. Biological trace element research."

Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: an animal model of autism.

"chronic metals exposure may contribute to the development of autism, possibly by interacting with central dopamine function, and support the use of prairie voles as a model organism in which to study autism."


CiteULike: Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: an animal model of autism.:

Developmental Immunotoxicity of Methylmercury: The Relative Sensitivity of Developmental and Immune Parameters

CiteULike: Developmental Immunotoxicity of Methylmercury: The Relative Sensitivity of Developmental and Immune Parameters: "relatively high sensitivity of the developing immune system and thereby illustrate the relevance of testing immune parameters in reproductive and developmental toxicity testing protocols"

Transition metals copper and iron in neurodegenerative diseases.

"interaction between metals and proteins in the nervous system seems to be a crucial factor for the development or absence of neurodegeneration. The present review also deals with the therapeutic strategies tested, mainly using metal chelating drugs. Metal accumulation within the nervous system observed in those diseases could be the result of compensatory mechanisms to improve metal availability for physiological processes"

Read more: CiteULike: The transition metals copper and iron in neurodegenerative diseases.:

Heavy Metals, Metallothionein and Regulation by Nrf2

Metallothionein: protein that modulates internal stores of heavy metals. Alterations in function have been recently implicated in autism as well as, other conditions where metals may be a factor including metabolic impairments and Alzheimer's.

In several past blogs, we have discussed health benefits of broccoli because it elevates the Nrf2 antioxidant system. In contrast to the preceding blog where it was noted that metallothioneins can inhibit GSK-3b which is an off/on switch for Nrf2 it has also be demonstrated that metalloproteins can be regulated by Nrf2. In 2005, Yeh's study suggested that sulphoraphane, "strongly suggest that at low concentrations of sulforaphane, activation of MAPKs such as ERK and p38 pathway lead to Nrf2-mediated metallothionein gene expression." One can assume from this that conditions that impair the Nrf2 system may lead to possible accumulation of toxic amounts of metals that can impair any number of metabolic processes. Such conditions include methylation, nutrition and other genetic factors such as polymorphisms, for example. Of course, this does not exclude factors that impair metallothionein on its own.

Notes:

• metallothionein expression needs to be tightly regulated because underexpression or overexpression can help mitigte or enhance disease.

HEIRS Library Tags: heavy metals, sulphoraphane (sulforaphane), Nrf2*****Sign up to receive alerts of heavy metal articles

            Blog Tags: Broccoli, sulforaphane, Nrf2

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Raymond, A. D., Gekonge, B., Giri, M. S., Hancock, A., Papasavvas, E., Chehimi, J., Kossevkov, A. V., Nicols, C., Yousef, M., Mounzer, K., Shull, J., Kostman, J., Showe, L., and Montaner, L. J. (2010). Increased metallothionein gene expression, zinc, and zinc-dependent resistance to apoptosis in circulating monocytes during hiv viremia. Journal of leukocyte biology.

http://www.citeulike.org/user/HEIRS/article/7369487


Yeh, C.-T. and Yen, G.-C. (2005). Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma hepg2 cells. Carginogenesis Advance Access.

http://www.citeulike.org/user/HEIRS/article/7369321

Sabolić, I., Breljak, D., Skarica, M., and Herak-Kramberger, C. M. (2010). Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine.

http://www.citeulike.org/user/HEIRS/article/7369302

TLRs Regulates Reactions to Particulate Matter and Other Contaminant Considerations~!

In this article, the author explains "it is plausible that PM2.5 contains bacterial or mycoplasma lipoproteins, which are known activators of TLR2 . Because PM2.5 contain high concentrations of a large number of metals. One or more of these metals could be involved in increased TLR2- mediated cytokine production triggered by microbial lipoprotein constituents of the PM2.5. In this regard, it is interesting that TLR2 has been implicated in proinflammatory cytokine expression by airway epithelial cells stimulated with air PM containing high amounts of metals. Another possibility is that PM2.5 cytokine-inducing effects are mediated by an indirect mechanism, via the generation of endogenous “danger” host molecules activating macrophages via TLR2."

Note: Recent findings by Notch show a potentiation effect between cyanobacteria and heavy metals and thus support an important mechanism although the mechanism remains to be elicited. In addition, one must always consider alterations in methylation which can be caused by endotoxin and heavy metals. Walsh and Usman demonstrated that in autism there is alterations in the functioning of metallotheinin protein which modulates and detoxifies metals. (Treat Autism and AD/HD, Wright) In other blogs, we have explained that metallotheinin inhibits GSK-3b (Wang)which can turn off the Nrf2 antioxidant system. This could explain why there are reports that the antioxidant system is negatively effected by metals (and by endotoxin)and thus, one must also consider that in mixed environmental pollutants, there is a reduction of function of this system. In addition, there is also potential that the AhR and metals interact to influence antioxidant and detoxification. These interactions of metals and the AhR are currently being investigated through a number of projects. (Korashy) Further study may shed more light on the interactions of the Nrf2 and AhR gene batteries and how they are effected by metals from environmental exposures.

Shoenfelt, J., Mitkus, R. J., Zeisler, R., Spatz, R. O., Powell, J., Fenton, M. J., Squibb, K. A., and Medvedev, A. E. (2009). Involvement of tlr2 and tlr4 in inflammatory immune responses induced by fine and coarse ambient air particulate matter. Journal of Leukocyte Biology, 86. http://www.citeulike.org/user/HEIRS/article/7367529

Vita. Hesham Korashy, PhD. Retrieved on June 29, 2010.
http://faculty.ksu.edu.sa/hkorashy/Pages/index.aspx

Notch, E. G., Miniutti, D. M., Berry, J. P., and Mayer, G. D. (2010). Cyanobacterial lps potentiates cadmium toxicity in zebrafish (danio rerio) embryos. Environmental toxicology.
http://www.citeulike.org/user/HEIRS/article/7367622

Heavy Metals. Treat Autism and ADHD. Retrieved on June 30, 2010. http://www.treatautism.ca/?page_id=126

Wang et al. Inactivation of GSK-3 by Metallothionein PreventsDiabetes-Related Changes in Cardiac EnergyMetabolism, Inflammation, Nitrosative Damage, and Remodeling. Diabetes. June 2009. Pgs. 1391-1402.

Wright, R. O. and Baccarelli, A. (2007). Metals and neurotoxicology. The Journal of Nutrition.
http://www.citeulike.org/user/HEIRS/article/7367642

Heavy Metals Elevates Antioxidant Capacity to Combat Oxidative Stress in Mine Workers~!

"Taken together, the results indicate that exposure to combination of Pb and Zn in mine elevates total antioxidant capacity of body in a reflex to overcome to oxidative stress. Especially, in the present case, it seems that toxic effect of Pb has been greater than positive effects of Zn, but the combination exposure has resulted in not such a critical toxicity situation."

CiteULike: Study on clinical and biochemical toxicity biomarkers in a zinc-lead mine workers:

Ascorbic Acid May Prevent Lead-Induced Hypertension via Nitric Oxide!

"ascorbic acid as an antioxidant prevents the lead induced hypertension. This effect may be mediated by inhibition of NOc oxidation and thereby increasing availability of NO."

Effect of ascorbic acid supplementation on nitric oxide metabolites and systolic blood pressure in rats exposed to lead Mohammad A, Ali N, Reza B, Ali K - Indian J Pharmacol:

Lactic acidosis from Heavy Metal Poisoning.

"Heavy metal toxicity, including poisoning with arsenic, can raise lactate levels and lead to generalized metabolic acidosis"

Lactic acidosis - Wikipedia, the free encyclopedia:

Ammonia Enzymes, Immune Cells & X-Linked Mutations In Autoimmunity and Disease

Background: We have suggested that environmental illnesses may involve the loss of suppression of regulatory T cells and that several different proteins may be involved which changes the dynamics or "immunological footprint" of these conditions in each individual. Previously we mentioned how high ammonia levels may account for some of the symptoms associated with multiple chemical sensitivity. We also noted recently how alterations in ornithine enzymes may effect ammonia levels and the Nrf2 gene regulator has some control over its expression. The following article discusses findings related to how a mutation in ornithine transcarbamalase may influence the immune system and play a role in autoimmune type disease. Interestingly, the author points out the condition is X-linked which might account for higher number of females presenting with them because males usually die in utero and do not live but a few days after birth. There is usually a large sexual dimorphism in the prevalence of many environmental diseases. As Li explains, there may be a number of factors that contribute to autoimmune disease which may include estrogenic production as well as, vulnerable phenotypes may be more susceptible to metals exposure which may accelerate some individuals to reactive phenotypes. (Li)

The author writes, "Antigen expression in the thymus leads to the deletion of self-reactive T cells and generation of regulatory lymphocytes, including regulatory T cells(Treg) and NKT cells. We show an Ornithine transcarbamylase(OTC) mutation causes ineffective presentation of self antigens in the thymus. As such, deletion of self reactive T cells is compromised and production of Treg and NKT cells is reduced in the OTC mutant mice. More importantly the heterozygous mice have increased susceptibility to autoimmune diseases, including the generation of autoantibodies and more severe EAE." Further, "OTC mutant mice, the production of Treg in the thymus is reduced, which is correlated with the impaired antigen presentation due to hyperammonemia."


Comment: This article is a good representation of why only qualified medical professionals that understand the multitude of genetic conditions and environmental conditions that activate them should be treating them. There is no evidence thus far, that a "therapeutic recipe" is effective at treating all of them.


Chang, X. (2006). X linked foxp3 & otc in immune tolerance and autoimmunity. Ohio State University. http://www.citeulike.org/user/HEIRS/article/6650098
Li, J., Stein, T. D., and Johnson, J. A. (2004). Genetic dissection of systemic autoimmune disease in nrf2 deficient mice. Physiological Genomics.
http://www.citeulike.org/user/HEIRS/article/6604948

Exposure to Metal-rich Particulate Matter Modifies the Expression of Candidate MicroRNAs in Peripheral Blood Leukocytes

CiteULike: Exposure to Metal-rich Particulate Matter Modifies the Expression of Candidate MicroRNAs in Peripheral Blood Leukocytes: "Bollati, V., Marinelli, B., Apostoli, P., Bonzini, M., Nordio, F., Hoxha, M., Pegoraro, V., Motta, V., Tarantini, L., Cantone, L., Schwartz, J., Bertazzi, P. A., and Baccarelli, A. (2010). Exposure to metal-rich particulate matter modifies the expression of candidate micrornas in peripheral blood leukocytes. Environmental Health Perspectives."

More Evidence of Metals Contributing Parkinson's Disease and Other Adverse Effects

CiteULike: A system-based comparison of gene expression reveals alterations in oxidative stress, disruption of ubiquitin-proteasome system and altered cell cycle regulation after exposure to cadmium and methylmercury in Mouse Embryonic Fibroblast (MEF): "Yu, X., Robinson, J. F., Sidhu, J. S., Hong, S., and Faustman, E. M. (2010). A system-based comparison of gene expression reveals alterations in oxidative stress, disruption of ubiquitin-proteasome system and altered cell cycle regulation after exposure to cadmium and methylmercury in mouse embryonic fibroblast (mef). Toxicol. Sci., pages kfq003+."

Childhood lead exposure causes permanent brain damage

A study using functional magnetic resonance imaging (fMRI) to evaluate brain function revealed that adults who were exposed to lead as children incur permanent brain injury. The results were presented today at the annual meeting of the Radiological Society of North America (RSNA).

LINK


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Quercetin can act either as an inhibitor or an inducer of the mitochondrial permeability transition pore: A demonstration of the ambivalent redox character of polyphenols.

"In swelling experiments with suspensions of mitochondria, high (20-50 microM) concentrations of quercetin, the most efficient inhibitor, promoted instead the onset of the MPT. Chelators of Fe(2+/3+) and Cu(+/2+) ions counteracted this effect. Fluorescent indicators of superoxide production confirmed that quercetin potentiates O(2)(*-) generation by isolated mitochondria and cultured cells. Since this was not affected by chelating Fe and Cu ions, the MPT-inducing effect can be ascribed to a "secondary", metal ion-catalyzed production of ROS."

De Marchi, U., Biasutto, L., Garbisa, S., Toninello, A., and Zoratti, M. (2009). Quercetin can act either as an inhibitor or an inducer of the mitochondrial permeability transition pore: A demonstration of the ambivalent redox character of polyphenols. Biochimica et biophysica acta, 1787(12):1425-1432. http://www.citeulike.org/user/HEIRS/article/5369424