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.

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            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