Resveratrol is a natural organic compound, polyphenol, produced naturally by some plants in response to several harmful factors such as attack by pathogens, UV radiation, or increased oxidative stress. Many experiments suggest that it triggers mechanisms that counteract aging-related effects and plays a role in insulin resistance as well. It also possesses beneficial properties such as anti-cancer, anti-inflammatory, blood-sugar-lowering and cardiovascular effects. It is supposed to exhibit an interesting activity in neuroprotection -mainly through activation of sirtuins and counteraction in forming peptide aggregates. Still research is needed to evaluate exactly how resveratrol protects neurons, and to develop new, potential, therapeutic drugs.List of abbreviations: Aβ -beta amyloid, ADAM 10 -protein belonging to the family of alpha-secretases, AKT -serine/threonine kinase Akt, AMPK -AMP-dependent kinase, ARE -the antioxidant response element, BDNF -brain derived neurotrophic factor, CaMKKβ -calmodulin-dependent protein kinase kinase β, cAMP -adenosine 3',5'-cyclic monophosphate, COX1 -cyclooxygenase 1, DRP1 -dynamin-related protein, Epac1 -guanine nucleotide exchange factor, F 2α (8-iso-PGF 2α ) -8-iso-prostaglandin F 2α , GSK-3β-β -glycogen synthase kinase 3, HD -Huntington's disease, HSF1 -heat shock factor, HSP-70 -heat shock protein, LDL -low density lipoproteins, MeCP2 -transcriptional protein, MFN1 -mitofusin 1, MFN2 -mitofusin 2, mPGES-1 -microsomal prostaglandin E synthase 1, MPTP-1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MsrA -methionine sulfoxide reductase, NEP -neprilysin, MyoD -myoblast determination protein 1, NF -kB -nuclear transcription factor, Nrf2 -nuclear factor 2, OH -1 -heme oxygenase 1, OPA1 -optic atrophy 1, PD -Parkinson's disease, PDE -phosphodiesterase cyclic nucleotides, PI3K -phosphatidylinositol 3-kinase, PGC-1α -proliferator peroxisome-activated receptor gamma coactivator 1-alpha , PGE 2 -prostaglandin E 2 , RAR -retinoic acid receptor β, RNS -reactive nitrogen species, ROCK -Rho-dependent kinase, ROS -reactive oxygen species, RSV -resveratrol, SIRT1 -sirtuin 1, SIRT3 -sirtuin 3, SOD -superoxide dismutase, TMS -2,3',4,5' tetramethylstilbene, TORC1 -target-of-rapamycin complex 1, YY1 -transcription factor Yin Yang 1 Brought to you by | CAPES Authenticated Download Date | 10/5/15 2:17 PM98 J. GERSZON, A. RODACKA, M. PUCHAŁA
The present study was aimed at investigating the effect of fullerenol C60(OH)36 on chosen parameters of the human erythrocyte membrane and the preliminary estimation of the properties of fullerenol as a potential linking agent transferring the compounds (e.g., anticancer drugs) into the membrane of erythrocytes. The results obtained in this study confirm the impact of fullerenol on erythrocyte cytoskeletal transmembrane proteins, particularly on the band 3 protein. The presence of fullerenol in each of the concentrations used prevented degradation of the band 3 protein. The results show that changes in the morphology of red blood cells caused by high concentrations of fullerenol (up to 150mg/L) did not lead to increased red blood cell hemolysis or the leakage of potassium. Moreover, fullerenol slightly prevented hemolysis and potassium efflux. The protective effect of fullerenol at the concentration of 150mg/L was 20.3%, and similar results were obtained for the efflux of potassium. The study shows that fullerenol slightly changed the morphology of the cells and, therefore, altered the intracellular organization of erythrocytes through the association with cytoskeletal proteins.
The influence of fullerenol on the activities of human erythrocyte membrane ATPases and the fluidity of the plasma membrane as well as the possibility of fullerenol incorporation into the plasma membrane were investigated. Fullerenol at concentrations up to 150 μg/mL induced statistically significant decreases in the anisotropy of 1-anilino-8-naphthalene sulfonate (ANS) (14%), N,N,N-trimethyl-4-(6-phenyl-1,3,5,-hexatrien-1-yl)phenylammonium p-toluenesulfonate (TMA-DPH) (7.5%) and 1,6-diphenyl-1,3,5-hexatriene (DPH) (9.5%) after a 1-hour incubation at 37°C. The effect disappeared for ANS and TMA-DPH, but not for DPH, after washing out the fullerenol. Incubation of erythrocyte membranes with fullerenol led to decreases in the activities of Na(+),K(+)-ATPase (to 23% of the control value), Ca(2+)-ATPase (to 16% of control) and Mg(2+)-ATPase (to 22% of control). Washing out the fullerenol lessened the inhibition of the Na(+),K(+)-ATPase (37% of control) and Ca(2+)-ATPase (23.5% of control); however, it did not influence Mg(2+)-ATPase activity. Furthermore, fullerenol could associate with erythrocyte plasma membranes. Our results suggest that fullerenol associates primarily with the surface of the plasma membrane; however, it can also migrate deeper inside the membrane. Moreover, fullerenol influences membrane ATPases so that it may modulate ion transport across membranes.
Human erythrocytes were exposed to gamma-rays and alpha-particles to assess radiation-induced membrane damage and hemoglobin oxidation and denaturation. With all parameters measured, the alpha-particles proved to be less efficient than the gamma-rays. The time-dependence of hemolysis showed also clear differences: with the gamma-rays the process was faster, reaching saturation after 40-90 min (depending on dose), but with the alpha-particles the final level was attained only after about 3-7 h. Hemoglobin oxidation and denaturation could be measured only after gamma-exposure, but they were negligible with the alpha-particles when comparable doses were applied. These results are interpreted by proposing that OH-radicals, whose yields are smaller with densely ionizing radiation, play a crucial role in the induction of the processes for radiation-induced erythrocyte damage.
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