The redox state of disulfide bonds is implicated in many redox control systems, such as the cysteine-cystine couple. Among proteins, ubiquitous cysteine-rich metallothioneins possess thiolate metal binding groups susceptible to metal exchange in detoxification processes. CeO2 NPs are commonly used in various industrial applications due to their redox properties. These redox properties that enable dual oxidation states (Ce(IV)/Ce(III)) to exist at their surface may act as oxidants for biomolecules. The interaction among metallothioneins, cysteine, and CeO2 NPs was investigated through various biophysical approaches to shed light on the potential effects of the Ce(4+)/Ce(3+) redox system on the thiol groups of these biomolecules. The possible reaction mechanisms include the formation of a disulfide bridge/Ce(III) complex resulting from the interaction between Ce(IV) and the thiol groups, leading to metal unloading from the MTs, depending on their metal content and cluster type. The formation of stable Ce(3+) disulfide complexes has been demonstrated via their fluorescence properties. This work provides the first evidence of thiol concentration-dependent catalytic oxidation mechanisms between pristine CeO2 NPs and thiol-containing biomolecules.
Risk Sohn, et al., pp. 1999Sohn, et al., pp. -2005 A particular genetic polymorphism can apparently decrease one's risk of colon cancer, yet increase risk of breast cancer. How does it work? Sohn et al. undertook to find out exactly what happens at the molecular level to induce this celltype-specific risk modification. They identified changes in intracellular folate cofactors resulting from the polymorphism that differ between colon and breast cancer cells, providing a possible explanation for the differences in risk.The mutation in question is a C677T polymorphism of the enzyme methylenetetrahydrofolate reductase, or MTHFR. Epidemiological evidence has mounted, indicating that this variant decreases the risk of several cancers, but increases the risk of others. No molecular evidence has yet provided a possible mechanism for this adjustment of risk, however. In the cell, MTHFR ensures the production of Sadenosylmethionine, or SAM, which is necessary for methylation of cytosine. Using an in vitro model of colon and breast cancer cells, the authors measured the concentrations of SAM and SAH (S-adenosylhomocysteine); they found that both were lessened, and the ratio of SAM to SAH was considerably lower in colon cancer cells expressing the mutant MTHFR than in those expressing the normal enzyme. In breast cancer cells, however, they found higher concentrations of both SAM and SAH in the cells expressing the mutant MTHFR, and the SAM-to-SAH ratio had increased by half. Similarly, the mutation upped homocysteine levels in colon cancer cells and lowered them in breast cancer cells. Overall genomic methylation, the team found, was increased by the mutation in colon cancer cell when the folate supply was high, but decreased when folate was scarce. In breast cancer cells, the mutation decreased genomic methylation when folate was abundant, but had no effect when folate was scarce.These results mark the first foray into puzzling out the molecular effects of the C677T polymorphism of MTHFR on various cancer cell types and provide the first plausible mechanism for how MTHFR affects risk differently in different cell types.l Compact Spheroid Formation Predicts Invasion Sodek, et al.. pp. 2060Sodek, et al.. pp. -2070 Ovarian cancer cells can form multicellular spheroid aggregates, a structure that protects the cancer cells from chemotherapeutic agents. But does this spheroid formation also assist in the spread of the cancer? Sodek et al. investigated this question by comparing 6 human ovarian cancer cell lines in their ability to form spheroids and their invasiveness and found a positive relationship between those two characteristics, suggesting that preventing spheroid formation could help beat back ovarian cancer.Not all ovarian cancers are created equal when it comes to spheroid formation, the authors found: of the 6 cell lines tested, 3 formed compact spheroids, while the others formed loose, sheet-like aggregates that never compacted.The lines that did form spheroids were also able to invade 3-D collagen matrices, while ...
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