Proteins effected by heavy metals and ionizing radiation

[Kathy]

New study on heavy metal toxicity out of Switzerland:

Biochem Biophys Res Commun. 2008 Jul 25;372(2):341-5. Epub 2008 May 21.

Heavy metal ions are potent inhibitors of protein folding.

Sharma SK, Goloubinoff P, Christen P.
Biochemisches Institut, Universität Zürich, CH-8057 Zürich, Switzerland.

Environmental and occupational exposure to heavy metals such as cadmium, mercury and lead results in severe health hazards including prenatal and developmental defects. The deleterious effects of heavy metal ions have hitherto been attributed to their interactions with specific, particularly susceptible native proteins. Here, we report an as yet undescribed mode of heavy metal toxicity. Cd2+, Hg2+ and Pb2+ proved to inhibit very efficiently the spontaneous refolding of chemically denatured proteins by forming high-affinity multidentate complexes with thiol and other functional groups (IC(50) in the nanomolar range). With similar efficacy, the heavy metal ions inhibited the chaperone-assisted refolding of chemically denatured and heat-denatured proteins. Thus, the toxic effects of heavy metal ions may result as well from their interaction with the more readily accessible functional groups of proteins in nascent and other non-native form. The toxic scope of heavy metals seems to be substantially larger than assumed so far.

PMID: 18501191

this study shows that interaction of fungus and heavy metals can result in the formation of metal crystals. Researchers in the prion field utilize yeast to create man-made prions. If they can make them with yeast - how is it they act so dense about how the are made in vivo?

Langmuir. 2005 Aug 2;21(16):7220-4.
Heavy-metal remediation by a fungus as a means of production of lead and cadmium carbonate crystals.

Sanyal A, Rautaray D, Bansal V, Ahmad A, Sastry M.
Nanoscience Group, Materials Chemistry and Biochemical Sciences Division, National Chemical Laboratory, Pune - 411 008, India.

We show here that reaction of the fungus, Fusarium oxysporum, with the aqueous heavy-metal ions Pb2+ and Cd2+ results in the one-step formation of the corresponding metal carbonates. The metal carbonates are formed by reaction of the heavy-metal ions with CO2 produced by the fungus during metabolism and thus provide a completely biological method for production of crystals of metal carbonates. The PbCO3 and CdCO3 crystals thus produced have interesting morphologies that are shown to arise because of interaction of the growing crystals with specific proteins secreted by the fungus during reaction. An additional advantage of this approach is that the reaction leads to detoxification of the aqueous solution and could have immense potential for bioremediation of heavy metals. Under conditions of this study, the metal ions are not toxic to the fungus, which readily grows after exposure to the metal ions.

PMID: 16042445

In the following, researchers are able to investigate the creation of prions using yeast, as a result of exposure to ionizing radiation from various products. Seems that there is evidence that the manufacturing process of the prion is KNOWN and that the main influencing factors are metals and radiation.

Radiation damage in biomolecular systems

In the Nuclear and Environmental Research Laboratory of the Institute of Physics, the radiation damage research started in 1980. Laboratory was involved in Chernobyl accident evaluation in terms of radioactive contamination and its influence on population. Numerous calculations and experiments on radiotoxicity and radiation level determination in INPP nuclear waste are performed until now. Concerning the radiation protection, measurements of radiation doses and contaminated source identification we have at our disposal the best available experimental basis in Lithuania.

The radiation induced damage in biomolecular systems is the new activity in the Nuclear Physics Department of Nuclear and Environmental Research Laboratory developed together with Vilnius University Plant Physiology and Microbiology department and within European cooperation in the field of scientific and technical research (COST Action P9).

In the Department of Plant Physiology and Microbiology of Vilnius University the biological structures such as yeast Saccharomyces cerevisiae are investigated. This unicellular microorganism is very convenient because of growth speed, fast reproduction cycle and metabolic signal pathways having many analogies in higher eukaryotes. One can affect the population of yeast by changing their environmental conditions (physical and chemical parameters) and observe the response of object - mutation or adaptation in a short period. The main controlling parameters are alterations in cell division, cell growth and evolution. The yeast mutants with a dysfunctional RAS/cAMP signal pathway are used. By this pathway the cell receives the signals from the growth environment. Mutations originating during the cell growth under extreme conditions determine differences in the activity of RAS/cAMP pathway.

The recent two years have been dedicated to investigation of yeast prions � proteins with altered conformation. Prions are the aggregated proteins which have lost their functions due to abnormal folding mutations. The analysis of the dynamics of proteins aggregation and it dependence on the RAS/cAMP pathway activity is performed. The environmental factors which have influence on prionization and/or prion elimination from the cells are being studied. At this point the apoptosis process � programmed death of the cell - is under investigation. Apoptosis is important for cancer cells treatment. It was pointed out, that prions provide adaptability for yeast cells and prevent apoptosis.

The study of the several phenomena related to the radiation effect on behavior of yeast systems is previewed by exposing it to ionizing radiation (α, b, g, X-ray and UV).

* Investigation of the different radiation kind and dose effect on cell vital regulation processes including cell sensitivity analysis at different stages of the cell cycle.

* Radiation effect on prionization, prion elimination in the yeast cells. The lethality of the prionic protein.

* The apoptosis phenomena.

The external or internal irradiation of the sample (yeast) by desired ionizing source is foreseen. It could be a strong α source such as 239Pu, b - 90Sr and g or X-ray sources depending on the desirable dose level. The first step of the research consists of irradiation of synchronized yeast cells by X-rays. Irradiation (depending on the dose) can be concentrated on different parts of the cell (nucleus or cytoplasm) and at different stages of the cell cycle. Cell is most sensitive to irradiation at the cell cycle division stage. Viability of the cell is observed control parameter.

For detailed calculation of the deposited ionizing radiation dose in the sample (cell and its surroundings) the available simulation codes are used. A simulation model of the ionizing source and the sample allows one to obtain the exact radiation dose rate received by the yeast (nucleus and cytoplasm) during the irradiation time. Calculations and the observation of the radiation-induced perturbation of normal physiological processes, along with the biological system responses, will help to understand the damage level: free radicals production, breakup of chemical bonds, new chemical bonds production or damage molecules that regulate vital cell processes.

Publications on investigations of Saccharomyces cerevisiae (Department of Plant Physiology and Microbiology of Vilnius University):

(see link for references)

http://www.fi.lt/directions/radbio.htm