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Modulation of adenosine receptors by [60]fullerene hydrosoluble derivative in SK-N-MC cells.

ABSTRACT: The most known fullerenes are spherical carbon compounds composed of 60 carbon atoms. C(60) fullerenes have shown biochemical and biomedical properties in the last years such as as blockade of apoptosis and neuroprotection. The nucleoside adenosine has a neuroprotective role mainly due to inhibition of glutamate release, which is a neurotransmitter related to excitotoxicity and cell death. In the present work, we have determined the presence of adenosine receptors in SK-N-MC cells, a neuroepithelioma human cell line, and analyzed the effect of fullerenes in these receptors by using radioligand binding, immunoblotting, and quantitative real time PCR assays. Results demonstrated that SK-N-MC cells endogenously express adenosine receptors. Fullerene exposure of these cells did not affect cell viability measured by MTT reduction assay. However, adenosine A(1) and A(2A) receptors were both increased in SK-N-MC cells after treatment. These results suggest for the first time the modulation of adenosine receptors after C(60) fullerenes exposure.

SUBMITTER: Giust D

PROVIDER: S-EPMC3369736 | biostudies-other | 2011 Jul

REPOSITORIES: biostudies-other

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Project description:The human body contains 60-70% water, depending on age. As a body fluid, it is not only a medium in which physical and chemical processes take place, but it is also one of the active mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by themselves (in vacuum), are diamagnetic but when organized into clusters, they become diamagnetic or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent hydrogen bonds in their structure. The interaction, as well as signal transmission, between water and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds, which determine the state and dynamics of conformational changes in biomolecules. Disruptive conformational changes in biomolecules, cells, and tissues lead to their dysfunctionality, so they are a frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance was developed based on the second derivative of the C60 molecule (SD-C60), which has classical and quantum properties. The characterization of SD-C60 by UV-VIS-NIR, FTIR, TEM, and AFM/MFM was performed and it is shown that SD-C60 water layers generate vibrations with near-zero phase dispersion which are transmitted through Fibonacci's water chains to biomolecules. In comparison with previously published SD-C60 derivate (3HFWC, size until 10 nm, and 1-5 water layers), the improved formulation (3HFWC-W, size 10-25 nm, and 6-9 water layers) showed multiplied cytotoxic activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action was preserved and based on an induction of senescence rather than cell death. Importantly, high selectivity towards malignant phenotypes was detected. Observed effects can be ascribed to a machinery of hydrogen bonds, which are generated in SD-C60 and transmitted through water to biomolecules. This approach may open a new field in science and healthcare-a "water-based nanomedicine".

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Modulation of adenosine receptors by [60]fullerene hydrosoluble derivative in SK-N-MC cells.

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