Selenium Reduces Mobile Phone (900 MHz)-Induced Oxidative Stress,Mitochondrial Function,and Apoptosis in Breast Cancer Cells

Exposure to mobile phone-induced electromagnetic radiation (EMR) may affect biological systems by increasing free oxygen radicals, apoptosis, and mitochondrial depolarization levels although selenium may modulate the values in cancer. The present study was designed to investigate the effects of 900 MHz radiation on the antioxidant redox system, apoptosis, and mitochondrial depolarization levels in MDA-MB-231 breast cancer cell line. Cultures of the cancer cells were divided into four main groups as controls, selenium, EMR, and EMR?+?selenium. In EMR groups, the cells were exposed to 900 MHz EMR for 1 h (SAR value of the EMR was 0.36?±?0.02 W/kg). In selenium groups, the cells were also incubated with sodium selenite for 1 h before EMR exposure. Then, the following values were analyzed: (a) cell viability, (b) intracellular ROS production, (c) mitochondrial membrane depolarization, (d) cell apoptosis, and (e) caspase-3 and caspase-9 values. Selenium suppressed EMR-induced oxidative cell damage and cell viability (MTT) through a reduction of oxidative stress and restoring mitochondrial membrane potential. Additionally, selenium indicated anti-apoptotic effects, as demonstrated by plate reader analyses of apoptosis levels and caspase-3 and caspase-9 values. In conclusion, 900 MHz EMR appears to induce apoptosis effects through oxidative stress and mitochondrial depolarization although incubation of selenium seems to counteract the effects on apoptosis and oxidative stress.     

Neuroprotective function of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, [R-(-)-BPAP], against apoptosis induced by N-methyl(R)salsolinol, an endogenous dopaminergic neurotoxin, in human dopaminergic neuroblastoma SH-SY5Y cells

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane HCl [R-(-)-BPAP] is one of "catecholaminergic and serotonergic enhancers", which were proposed to improve symptoms through increase in impulse-evoked release of monoamine neurotransmitters for Parkinson's disease. It was reported that (-)-BPAP up-regulated the synthesis of neurotrophic factors in mouse astrocytes, suggesting the neuroprotective potency of (-)-BPAP. In this paper, the neuroprotective function of (-)-BPAP and the related compounds was examined against apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol [NM(R)Sal], a possible pathogenic toxin in Parkinson's disease, in human dopaminergic neuroblastoma SH-SY5Y cells. The anti-apoptotic activity was confirmed with some of (-)-BPAP analogues, and the mechanism was found to be due to the direct stabilization of mitochondrial membrane potential and the induction of anti-apoptotic Bcl-2. The studies on structure-activity relationship demonstrated that the potency to stabilize the mitochondrial membrane potential depended on the absolute stereo-chemical structure of BPAP derivatives. The compounds with dextrorotation prevented the mitochondrial permeability transition, whereas those with levorotation did not. The presence of a propargyl or propyl group at the amino residue of R-(-)-1-(benzofuran-2-yl)-2-propylamine increased potency to stabilize the membrane potential and prevent apoptosis. R-FPFS-1169 and R-FPFS-1180 had more potent to induce Bcl-2 and prevent apoptosis than the corresponding S-enantiomers. These results are discussed with the possible application of BPAP derivatives as neuroprotective agents in Parkinson's disease and other neurodegenerative disorders.     

Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain,kidney and liver oxidative stress and some biochemical parameters in male rats

Abstract

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1?h/d for 60?d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1?h/d for 60?d then left for 30?d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p?<?0.05), while serum catecholamines were insignificantly higher in the exposed rats. These alterations were corrected by withdrawal. In conclusion, electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.     

Effect of 3G Cell Phone Exposure with Computer Controlled 2-D Stepper Motor on Non-thermal Activation of the hsp27/p38MAPK Stress Pathway in Rat Brain

Cell phone radiation exposure and its biological interaction is the present concern of debate. Present study aimed to investigate the effect of 3G cell phone exposure with computer controlled 2-D stepper motor on 45-day-old male Wistar rat brain. Animals were exposed for 2 h a day for 60 days by using mobile phone with angular movement up to zero to 30°. The variation of the motor is restricted to 90° with respect to the horizontal plane, moving at a pre-determined rate of 2° per minute. Immediately after 60 days of exposure, animals were scarified and numbers of parameters (DNA double-strand break, micronuclei, caspase 3, apoptosis, DNA fragmentation, expression of stress-responsive genes) were performed. Result shows that microwave radiation emitted from 3G mobile phone significantly induced DNA strand breaks in brain. Meanwhile a significant increase in micronuclei, caspase 3 and apoptosis were also observed in exposed group (P < 0.05). Western blotting result shows that 3G mobile phone exposure causes a transient increase in phosphorylation of hsp27, hsp70, and p38 mitogen-activated protein kinase (p38MAPK), which leads to mitochondrial dysfunction-mediated cytochrome c release and subsequent activation of caspases, involved in the process of radiation-induced apoptotic cell death. Study shows that the oxidative stress is the main factor which activates a variety of cellular signal transduction pathways, among them the hsp27/p38MAPK is the pathway of principle stress response. Results conclude that 3G mobile phone radiations affect the brain function and cause several neurological disorders.     

Neuroprotective effects of mercaptoethylleonurine and mercaptoethylguanidine analogs on hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells

A series of mercaptoethylleonurine and mercaptoethylguanidine derivatives were designed and synthesized. Their neuroprotective effects toward H₂O₂-induced apoptosis were investigated in human SH-SY5Y cells. The results from these studies identified several potent compounds, with compound 8k emerging as the most effective. Further investigation demonstrated that 8k reduced H₂O₂-induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of Bcl-2. Moreover, the molecular mechanism underlying the observed neuroprotective effects of 8k was exerted via the Akt and JNK pathways. Compound 8k can be a lead compound for further discovery of neuroprotective medicine.     

BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins

Release of apoptogenic proteins such as cytochrome c from mitochondria is regulated by pro- and anti-apoptotic Bcl-2 family proteins, with pro-apoptotic BH3-only proteins activating Bax and Bak. Current models assume that apoptosis induction occurs via the binding and inactivation of anti-apoptotic Bcl-2 proteins by BH3-only proteins or by direct binding to Bax. Here, we analyze apoptosis induction by the BH3-only protein Bim(S). Regulated expression of Bim(S) in epithelial cells was followed by its rapid mitochondrial translocation and mitochondrial membrane insertion in the absence of detectable binding to anti-apoptotic Bcl-2 proteins. This caused mitochondrial recruitment and activation of Bax and apoptosis. Mutational analysis of Bim(S) showed that mitochondrial targeting, but not binding to Bcl-2 or Mcl-1, was required for apoptosis induction. In yeast, Bim(S) enhanced the killing activity of Bax in the absence of anti-apoptotic Bcl-2 proteins. Thus, cell death induction by a BH3-only protein can occur through a process that is independent of anti-apoptotic Bcl-2 proteins but requires mitochondrial targeting.     

Paeoniflorin, a Natural Neuroprotective Agent, Modulates Multiple Anti-Apoptotic and Pro-apoptotic Pathways in Differentiated PC12 Cells

Numerous studies have shown robust neuroprotective effects of paeoniflorin (PF), a natural compound derived from the herbal medicine Paeony radix. In the present study, we determined associations of PF neuroprotection with its modulation of various apoptotic and anti-apoptotic pathways. PF (50–400 μM) pretreatment significantly improved viability of differentiated PC12 cells exposed to methyl-4-phenylpyridine ion (MPP⁺), a neurotoxin, and inhibited over-release of lactate dehydrogenase, a biomarker of neuronal cell death. PF also ameliorated MPP⁺-induced nuclear and mitochondrial apoptotic alteration and intracellular calcium overload. PF treatment reversed MPP⁺ suppression of activity of B cell lymphoma-extra large, which is a mitochondrial membrane molecule that protects cells from DNA damage-induced apoptosis, and strikingly inhibited the enhanced level of cleaved poly(ADP-ribose)polymerase, which is involved in the process of apoptosis. PF alone and coadministration with MPP⁺ enhanced phospho activation of extracellular signal-regulated kinases, Akt, and its downstream element glycogen synthase kinase-3, but the effects were completely abolished in the presence of their blockers PD98059 and LY294002. The presence of the blockers also diminished the potency of PF in improving viability of MPP⁺-exposed cells. These results indicate that neuroprotective effects of PF are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways, including blockade of intracellular calcium overload, prevention of mitochondrial membrane integrity, inhibition of pro-apoptotic molecules, and up-regulation of anti-apoptotic proteins associated with cell survival and proliferation. The study provides evidence supporting PF as a potential therapeutic agent used for the treatment of neurodegenerative diseases and neural injury.     

Synthesis and discovery of a novel pyrazole derivative as an inhibitor of apoptosis through modulating integrin beta4, ROS, and p53 levels in vascular endothelial cells

Recently, pyrazole derivatives as high affinity and selective A2A adenosine receptor antagonists have been reported. But, so far, there are no reports about the inhibitory effects of multi-substituted pyrazole derivatives on apoptosis of vascular endothelial cells (VECs). In this study, we synthesized six pyrazole derivatives and characterized the structures of the compounds by IR, ¹H NMR, mass spectroscopy, and element analysis. The biology assay showed that a novel pyrazole derivative, ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (MPD) at low concentration (25 μM) increased VECs viability and inhibited VECs apoptosis induced by deprivation of serum and FGF-2. During this process, the levels of integrin β4, reactive oxygen species (ROS), and p53 were depressed obviously. The data suggested that MPD was a potential inhibitor of apoptosis associated with the signal pathway mediated by integrin β4, ROS, and p53 in VECs.     

A highly bioactive lignophenol derivative from bamboo lignin exhibits a potent activity to suppress apoptosis induced by oxidative stress in human neuroblastoma SH-SY5Y cells

Approaches to protection against neurodegenerative diseases, in which oxidative stress and inflammation are implicated, should be based on the current concept on the etiology of these diseases. Recently, a new therapeutic strategy has been proposed to protect neurons from cell death by attenuating the apoptotic signal transduction. Lignin, a durable aromatic network polymer second to cellulose in abundance, was able to be converted into highly active lignophenol derivatives with antioxidant activity by using our newly developed phase-separation technique. These lignophenol derivatives were found to show the potent neuroprotective activity against oxidative stress. Among the compounds examined, a lignocresol derivative from bamboo (lig-8) exhibited the most potent neuroprotective activity against hydrogen peroxide (H(2)O(2))-induced apoptosis in human neuroblastoma cell line SH-SY5Y by preventing the caspase-3 activation via either caspase-8 or caspase-9. Furthermore, it was found that lig-8 exerted the antiapoptotic effect by inhibiting dissipation of the mitochondrial membrane permeability transition induced by H(2)O(2) or by the peripheral benzodiazepin receptor ligand PK11195. Lig-8 was also shown to be potent in the antioxidant activity in the cells exposed to H(2)O(2), as assessed by flow cytometry using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and in vitro reactive oxygen species-scavenging potency. These data suggest that lig-8 is a promising neuroprotector, which affects the signaling pathway of neuronal cell death and that it would be of benefit to delay the progress of neurodegenerative diseases.     

In vitro exposure of human lymphocytes to 900 MHz CW and GSM modulated radiofrequency: studies of proliferation, apoptosis and mitochondrial membrane potential

The aim of this study was to investigate the nonthermal effects of radiofrequency (RF) fields on human immune cells exposed to a Global System for Mobile Communication (GSM) signal generated by a commercial cellular phone and by a sinusoidal non-modulated signal. To assess whether mobile phone RF-field exposure affects human immune cell functions, peripheral blood mononuclear cells (PBMCs) from healthy donors were exposed in vitro to a 900 MHz GSM or continuous-wave (CW) RF field 1 h/day for 3 days in a transverse electromagnetic mode (TEM) cell system (70-76 mW/kg average specific absorption rate, SAR). The cells were cultured for 48 or 72 h, and the following end points were studied: (1) mitogen-induced proliferation; (2) cell cycle progression; (3) spontaneous and 2-deoxy-D-ribose (dRib)-induced apoptosis; (4) mitochondrial membrane potential modifications during spontaneous and dRib-induced-apoptosis. Data obtained from cells exposed to a GSM-modulated RF field showed a slight decrease in cell proliferation when PBMCs were stimulated with the lowest mitogen concentration and a slight increase in the number of cells with altered distribution of phosphatidylserine across the membrane. On the other hand, cell cycle phases, mitochondrial membrane potential and susceptibility to apoptosis were found to be unaffected by the RF field. When cells were exposed to a CW RF field, no significant modifications were observed in comparison with sham-exposed cells for all the end points investigated.     

Protective effects of melatonin and caffeic acid phenethyl ester against retinal oxidative stress in long-term use of mobile phone: A comparative study

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the efficacy of the protective effects of melatonin and CAPE against retinal oxidative stress due to long-term exposure to 900 MHz EMR emitting mobile phones. Melatonin and CAPE were administered daily for 60 days to the rats prior to their EMR exposure during our study. Nitric oxide (NO, an oxidant product) levels and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of retinal oxidative stress in rats following to use of EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in retinal tissue. Retinal levels of NO and MDA increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of NO and MDA. Likewise, retinal SOD, GSH-Px and CAT activities decreased in EMR exposed animals while melatonin and CAPE caused a significant increase in the activities of these antioxidant enzymes. Treatment of EMR exposed rats with melatonin or CAPE increased the activities of SOD, GSH-Px and CAT to higher levels than those of control rats. In conclusion, melatonin and CAPE reduce retinal oxidative stress after long-term exposure to 900 MHz emitting mobile phone. Nevertheless, there was no statistically significant difference between the efficacies of these two antioxidants against to EMR induced oxidative stress in rat retina. The difference was in only GSH-Px activity in rat retina. Melatonin stimulated the retinal GSH-Px activity more efficiently than CAPE did.     

Evidence for mobile phone radiation exposure effects on reproductive pattern of male rats: Role of ROS

The relationship between radiofrequency electromagnetic fields emitted from mobile phone and infertility is a matter of continuing debate. It is postulated that these radiations may affect the reproduction pattern spell by targeting biochemistry of sperm. In an attempt to expedite the issue, 70 days old Wistar rats (n?=?6) were exposed to mobile phone radiofrequency (RF) radiation for 2?h per day for 45 days and data compared with sham exposed (n?=?6) group. A significant decrease (P?相似文献   

Book Review

Abstract

To investigate the potential adverse effects of mobile phone radiation, we studied reactive oxygen species (ROS), DNA damage and apoptosis in mouse embryonic fibroblasts (NIH/3T3) after intermittent exposure (5?min on/10?min off, for various durations from 0.5 to 8?h) to an 1800-MHz GSM-talk mode electromagnetic radiation (EMR) at an average specific absorption rate of 2?W/kg. A 2′,7′-dichlorofluorescin diacetate fluorescence probe was used to detect intracellular ROS levels, immunofluorescence was used to detect γH2AX foci as a marker for DNA damage, and flow cytometry was used to measure apoptosis. Our results showed a significant increase in intracellular ROS levels after EMR exposure and it reached the highest level at an exposure time of 1?h (p?p?相似文献   

Structure-activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives

Gallic acid and its derivatives are a group of naturally occurring polyphenol antioxidants which have recently been shown to have potential healthy effects. In order to understand the relationship between the structures of gallic acid derivatives, their antioxidant activities, and neuroprotective effects, we examined their free radical scavenging effects in liposome and anti-apoptotic activities in human SH-SY5Y cell induced by 6-hydrodopamine autooxidation. It was found that these polyphenol antioxidants exhibited different hydrophobicity and could cross through the liposome membrane to react with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical in a time and dose-dependent manner. At the same time, the structure-antioxidant activity relationship of gallic acid derivatives on scavenging DPPH free radical in the liposome was also analyzed based on theoretical investigations. Analysis of cell apoptosis, intracellular GSH levels, production of ROS and the influx of Ca(2+) indicated that the protective effects of gallic acid derivatives in cell systems under oxidative stress depend on both their antioxidant capacities and hydrophobicity. However, the neuroprotective effects of gallic acid derivatives seem to depend more on their molecular polarities rather than antioxidant activities in the human SH-SY5Y cell line. In conclusion, these results reveal that compounds with high antioxidant activity and appropriate hydrophobicity are generally more effective in preventing the injury of oxidative stress in neurodegenerative diseases.     

Design and synthesis of 4-alkynyl pyrazoles as inhibitors of PDE4: a practical access via Pd/C-Cu catalysis

The design and synthesis of 4-alkynyl pyrazole derivatives has led to the identification of new class of PDE4 inhibitors. All these compounds were accessed for the first time via a facile Pd/C-CuI-PPh(3) mediated C-C bond forming reaction between an appropriate pyrazole iodide and various terminal alkynes. In vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized indicated that 4-alkynyl pyrazole could be a promising template for the discovery of novel PDE4 inhibitors.     

Evidence for mobile phone radiation exposure effects on reproductive pattern of male rats: Role of ROS

The relationship between radiofrequency electromagnetic fields emitted from mobile phone and infertility is a matter of continuing debate. It is postulated that these radiations may affect the reproduction pattern spell by targeting biochemistry of sperm. In an attempt to expedite the issue, 70 days old Wistar rats (n = 6) were exposed to mobile phone radiofrequency (RF) radiation for 2 h per day for 45 days and data compared with sham exposed (n = 6) group. A significant decrease (P < 0.05) in the level of testosterone and an increase in caspase-3 activity were found in the RF-exposed animals. Distortions in sperm head and mid piece of sperm mitochondrial sheath were also observed as captured by Transmission Electron Microscope (TEM). In addition, progeny from RF-exposed rats showed significant decreases in number and weight as compared with that of sham-exposed animals. A reduction in testosterone, an increase in caspase-3, and distortion in spermatozoa could be caused by overproduction of reactive oxygen species (ROS) in animals under mobile phone radiation exposure. Our findings on these biomarkers are clear indications of possible health implications of repeated exposure to mobile phone radiation.     

Red wine polyphenols prevent cyclosporine-induced nephrotoxicity at the level of the intrinsic apoptotic pathway

Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether Provinols flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with Provinols, or with CsA and Provinols simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. Provinols restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms.     

Pre-conditioning induced by carbon monoxide provides neuronal protection against apoptosis

Carbon monoxide (CO) is an endogenous product of mammalian cells generated by heme-oxygenase, presenting anti-apoptotic properties in several tissues. The present work demonstrates the ability of small amounts of exogenous CO to prevent neuronal apoptosis induced by excitotoxicity and oxidative stress in mice primary culture of cerebellar granule cells. Additionally, our data show that endogenous CO is a heme-oxygenase product critical for its anti-apoptotic activity. Despite being neuroprotective, CO also induces reactive oxygen species generation in neurons. These two phenomena suggest that CO induces pre-conditioning (PC) to prevent cell death. The role of several PC mediators, namely soluble guanylyl cyclase, nitric oxide (NO) synthase, and ATP-dependent mitochondrial K channel (mitoK(ATP)) was addressed. Inhibition of soluble guanylyl cyclase or NO synthase activity, or closing of mitoK(ATP) abolishes the protective effect conferred by CO. In addition, CO treatment triggers cGMP and NO production in neurons. Opening of mitoK(ATP), which appears to be critical for CO prevention of apoptosis, might be a later event. We also demonstrated that reactive oxygen species generation and de novo protein synthesis are necessary for CO PC effect and neuroprotection. In conclusion, CO induces PC and prevents neuronal apoptosis, therefore constituting a novel and promising candidate for neuroprotective therapies.     

Bcl-2 family members localize to tobacco chloroplasts and inhibit programmed cell death induced by chloroplast-targeted herbicides

In mammalian cells, apoptosis is often mediated via organelles. While apoptotic-like cell death occurs in plants, the mechanistic details are unresolved. Transgenic tobacco plants have been generated that harbour selected animal anti-apoptotic genes. Subcellular fractionation followed by western blot analysis indicated that chloroplasts serve as a location for these animal anti-apoptotic proteins in addition to the established mitochondrial location. To explore the functional significance of this observation, tobacco plants were treated with three chloroplast-directed herbicides. Wild-type plants died and exhibited features associated with apoptosis. Transgenic plants survived and did not show any apoptotic-like characteristics. Moreover, the herbicide-induced apoptotic-like cell death was light requiring. It was concluded that chloroplasts may be involved in mediating certain types of plant programmed cell death.