Nonthermal induction of heat shock protein 70 and heterogeneous nuclear ribonucleoprotein K are involved in the stress reaction of human lens epithelial cells to electromagnetic fields.

PMID: 

Jpn J Ophthalmol. 2007 Nov-Dec;51(6):412-6. Epub 2007 Dec 21. PMID: 18158590

Abstract Title: 

Proteomic analysis of human lens epithelial cells exposed to microwaves.

Abstract: 

PURPOSE: To study proteomic changes in human lens epithelial cells (HLECs) exposed to 1800-MHz Global System for Mobile Communication (GSM)-like microwaves.METHODS: In three separate experiments, HLECs were exposed and sham-exposed (six dishes each) to 1800-MHz GSM-like radiation for 2 h. The specific absorption rates were 1.0, 2.0, or 3.5 W/kg. Immediately after radiation, the proteome was extracted from the HLECs. Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis(2-DE; silver staining) and PDQuest 2-DE analysis software were used to separate and analyze the proteome of exposed and sham-exposed HLECs. Four differentially expressed protein spots were selected and identified by using electrospray ionization tandem mass spectrometry (ESI-MS-MS).RESULTS: When the protein profiles of exposed cells were compared with those of sham-exposed cells, four proteins were detected as upregulated. After analysis by ESI-MS-MS and through a database search, heat-shock protein (HSP) 70 and heterogeneous nuclear ribonucleoprotein K (hnRNP K) were determined to be upregulated in the exposed cells.CONCLUSIONS: Two-dimensional polyacrylamide gel electrophoresis combined with mass spectrometry may be a powerful tool for screening potential electromagnetic-reaction protein markers. HSP70 and hnRNP K are involved in the stress reaction of HLECs exposed to microwaves. These cell responses are nonthermal effects of the electromagnetic field.

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Activation of heat shock protein 27 pathway may be a mechanism that underpins the electromagnetic field-cancer connection.

PMID: 

Differentiation. 2002 May ;70(2-3):120-9. PMID: 12076339

Abstract Title: 

Non-thermal activation of the hsp27/p38MAPK stress pathway by mobile phone radiation in human endothelial cells: molecular mechanism for cancer- and blood-brain barrier-related effects.

Abstract: 

We have examined whether non-thermal exposures of cultures of the human endothelial cell line EA.hy926 to 900 MHz GSM mobile phone microwave radiation could activate stress response. Results obtained demonstrate that 1-hour non-thermal exposure of EA.hy926 cells changes the phosphorylation status of numerous, yet largely unidentified, proteins. One of the affected proteins was identified as heat shock protein-27 (hsp27). Mobile phone exposure caused a transient increase in phosphorylation of hsp27, an effect which was prevented by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase (p38MAPK). Also, mobile phone exposure caused transient changes in the protein expression levels of hsp27 and p38MAPK. All these changes were non-thermal effects because, as determined using temperature probes, irradiation did not alter the temperature of cell cultures, which remained throughout the irradiation period at 37 +/- 0.3 degrees C. Changes in the overall pattern of protein phosphorylation suggest that mobile phone radiation activates a variety of cellular signal transduction pathways, among them the hsp27/p38MAPK stress response pathway. Based on the known functions of hsp27, we put forward the hypothesis that mobile phone radiation-induced activation of hsp27 may (i) facilitate the development of brain cancer by inhibiting the cytochrome c/caspase-3 apoptotic pathway and (ii) cause an increase in blood-brain barrier permeability through stabilization of endothelial cell stress fibers. We postulate that these events, when occurring repeatedly over a long period of time, might become a health hazard because of the possible accumulation of brain tissue damage. Furthermore, our hypothesis suggests that other brain damaging factors may co-participate in mobile phone radiation-induced effects.

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Radiofrequency fields at 2.45 GHz can alter gene expression in human cells by a non-thermal mechanism.

PMID: 

Mutat Res. 2013 Jan 20 ;750(1-2):27-33. Epub 2012 Oct 8. PMID: 23059817

Abstract Title: 

Comparison of cytotoxic and genotoxic effects of plutonium-239 alpha particles and mobile phone GSM 900 radiation in the Allium cepa test.

Abstract: 

The goal of this study was to compare the cytotoxic and genotoxic effects of plutonium-239 alpha particles and GSM 900 modulated mobile phone (model Sony Ericsson K550i) radiation in the Allium cepa test. Three groups of bulbs were exposed to mobile phone radiation during 0 (sham), 3 and 9h. A positive control group was treated during 20min with plutonium-239 alpha-radiation. Mitotic abnormalities, chromosome aberrations, micronuclei and mitotic index were analyzed. Exposure to alpha-radiation from plutonium-239 and exposure to modulated radiation from mobile phone during 3 and 9h significantly increased the mitotic index. GSM 900 mobile phone radiation as well as alpha-radiation from plutonium-239 induced both clastogenic and aneugenic effects. However, the aneugenic activity of mobile phone radiation was more pronounced. After 9h of exposure to mobile phone radiation, polyploid cells, three-groups metaphases, amitoses and some unspecified abnormalities were detected, which were not registered in the other experimental groups. Importantly, GSM 900 mobile phone radiation increased the mitotic index, the frequency of mitotic and chromosome abnormalities, and the micronucleus frequency in a time-dependent manner. Due to its sensitivity, the A. cepa test can be recommended as a useful cytogenetic assay to assess cytotoxic and genotoxic effects of radiofrequency electromagnetic fields.

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Probiotic kefir was able to attenuate the molecular, structural, and physiological cardiovascular changes induced by BPA.

PMID: 

J Nutr Biochem. 2019 Oct 25 ;75:108254. Epub 2019 Oct 25. PMID: 31707283

Abstract Title: 

Bisphenol A contamination in infant rats: molecular, structural, and physiological cardiovascular changes and the protective role of kefir.

Abstract: 

The effects of bisphenol A (BPA) contamination on the cardiovascular function still are not clear. Here, we evaluated the vascular effects of BPA and the protective actions of kefir in infant rats. Animals (25 days old) were treated with BPA (100μg/Kg/day) for 60 days (BPA group), or administered kefir (0.3 mL/100 g) in addition to BPA (BPA kefir group), compared with non-treated rats (Control group).The vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine and specific blockers. The balance between reactive oxygen species (ROS) and nitric oxide (NO) was assessed through flow cytometry in the vascular tissue. The BPA group developed high blood pressure (+10%) and the analysis of vascular reactivity showed an impaired ACh-induced relaxation (~80%). The further analysis by using NADPH, NOS and COX blockers revealed that the impaired vasorelaxation was due to increased ROS production (+12%), NO bioavailability (-12%) and increased vasoconstriction to prostanoids (+36%) compared with the Control group. Kefir treatment reverted those effects significantly. Analysis of the aorticcells showed increased •Oproduction (1942±39 a.u.) and decreased NO bioavailability (1250±30 a.u.) compared with the Control group (1374±146 and 2777±25 a.u., P

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Paeonol has significantly growth-inhibitory and apoptosis-inducing effects in gastric cancer cells both in vitro and in vivo.

PMID: 

World J Gastroenterol. 2010 Sep 21 ;16(35):4483-90. PMID: 20845518

Abstract Title: 

Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo.

Abstract: 

AIM: To investigate the anti-tumor effects of paeonol in gastric cancer cell proliferation and apoptosis in vitro and in vivo.METHODS: Murine gastric cancer cell line mouse forestomach carcinoma (MFC) or human gastric cancer cell line SGC-7901 was cultured in the presence or absence of paeonol. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell cycle and apoptosis by flow cytometry and TUNEL staining. Tumor growth after subcutaneous implantation of MFC cells in mice was monitored, and the effects of treatment with paeonol were determined.RESULTS: In vitro, paeonol caused dose-dependent inhibition on cell proliferation and induced apoptosis. Cell cycle analysis revealed a decreased proportion of cells in G0/G1 phase, with arrest at S. Paeonol treatment in gastric cancer cell line MFC and SGC-790 cells significantly reduced the expression of Bcl-2 and increased the expression of Bax in a concentration-related manner. Administration of paeonol to MFC tumor-bearing mice significantly lowered the tumor growth and caused tumor regression.CONCLUSION: Paeonol has significantly growth-inhibitory and apoptosis-inducing effects in gastric cancer cells both in vitro and in vivo.

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Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma.

PMID: 

Can J Physiol Pharmacol. 2010 Oct ;88(10):1010-6. PMID: 20962901

Abstract Title: 

Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma.

Abstract: 

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γlevels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

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Paeonol attenuates hydrogen peroxide-induced NF-κB-associated amyloid precursor protein expression.

PMID: 

Am J Chin Med. 2010 ;38(6):1171-92. PMID: 21061469

Abstract Title: 

Paeonol attenuates H₂O₂-induced NF-κB-associated amyloid precursor protein expression.

Abstract: 

Hydrogen peroxide (H₂O₂) has been shown to promote neurodegeneration by inducing the activation of nuclear factor-κB (NF-κB). In this study, NF-κB activation was induced by H₂O₂ in human neuroblastoma SH-SY5Y cells. Whether paeonol, one of the phenolic phytochemicals isolated from the Chinese herb Paeonia suffruticosa Andrews (MC), would attenuate the H₂O₂-induced NF-κB activity was investigated. Western blot results showed that paeonol inhibited the phosphorylation of IκB and the translocation of NF-κB into the nucleus. The ability of paeonol to reduce DNA binding ability and suppress the H₂O₂-induced NF-κB activation was confirmed by an electrophoretic mobility shift assay and a luciferase reporter assay. Using a microarray combined with gene set analysis, we found that the suppression of NF-κB was associated with mature T cell up-regulated genes, the c-jun N-terminal kinase pathway, and two hypoxia-related gene sets, including the hypoxia up-regulated gene set and hypoxia inducible factor 1 targets. Moreover, using network analysis to investigate genes that were altered by H₂O₂ and reversely regulated by paeonol, we found that NF-κB was the primary center of the networkand amyloid precursor protein (APP) was the secondary center. Western blotting showed that paeonol inhibited APP at the protein level. In conclusion, our work suggests that paeonol down-regulates H₂O₂-induced NF-κB activity, as well as NF-κB-associated APP expression. Furthermore, the gene expression profile accompanying the suppression of NF-κB by paeonol was identified. The new gene set that can be targeted by paeonol provided a potential use for this drug and a possible pharmacological mechanism for other phenolic compounds that protect against oxidative-related injury.

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Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer’s disease.

PMID: 

Brain Res. 2011 May 4 ;1388:141-7. Epub 2011 Mar 4. PMID: 21377451

Abstract Title: 

Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer's disease.

Abstract: 

Paeonol(2'-hydroxy-4'-methoxyacetophenone;1-(2-hydroxy-4-methoxyphenyl)ethan-1-one) is a constituent of the bark of the Moutan Cortex (Paeonia suffruticosa). This bark has been used as a traditional Chinese medicine and is reputed to possess a broad range of therapeutic properties probably by virtue of its anti-inflammatory and free radical scavenging properties. The effects of paeonol on a variety of biochemical and behavioral parameters were studied in rat brain in rat brain after experimental animals had been subjected to an intra-hippocampal injection of amyloid peptide, Aβ1-42. Sprague-Dawley rats were randomly divided into groups: saline, sham operated, β-amyloid (Aβ)-injected (intended to model Alzheimer's disease, (AD), and a group receiving both injected amyloid peptide and paeonol. Forty days after intra-hippocampal injection, H&E staining revealed that the lesions in the paeonol-treated group were significantly less than the untreated group. Levels of cytochrome oxidase andα-actin, determined immunohistochemically, were elevated in the paeonol treated group relative to the group receiving amyloid peptide alone. TUNEL staining revealed more apoptotic cells in the walls of the cerebral vascular elements in the AD model group than in the paeonol group. The paeonol-treated group also showed improvement in behavioral indices of learning relative to the group receiving Aβ1-42 alone, as judged using a Y-type electric maze. Treatment with paeonol can protect against many of the alterations resulting from administration of Aβ1-42. in a rat model of AD. These include morphological, biochemical and behavioral changes. Paeonol is a possible therapeutic measure in slowing down the pathogenic processes associated with AD.

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Paeonol protects memory after ischemic stroke via inhibiting β-secretase and apoptosis.

PMID: 

Evid Based Complement Alternat Med. 2012 ;2012:932823. Epub 2012 Mar 13. PMID: 22474531

Abstract Title: 

Paeonol Protects Memory after Ischemic Stroke via Inhibitingβ-Secretase and Apoptosis.

Abstract: 

Poststroke dementia commonly occurs following stroke, with its pathogenesis related toβ-amyloid production and apoptosis. The present study evaluate the effects of paeonol, one of the phenolic phytochemicals isolated from the Chinese herb Paeonia suffruticosa Andrews (MC), on protection from memory loss after ischemic stroke in the subacute stage. Rats were subjected to transient middle cerebral artery occlusion (tMCAo) with 10 min of ischemia. The data revealed that paeonol recovered the step-through latency in the retrieval test seven days after tMCAo, but did not improve the neurological deficit induced by tMCAo. Levels of Amyloid precursor protein (APP)- and beta-site APP cleaving enzyme (BACE; β-secretase)-immunoreactive cells, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells decreased in the paeonol-administered group. Western blotting revealed decreased levels of Bax protein in mitochondria and apoptosis-inducing factor (AIF) in cytosol following paeonol treatment. In conclusion, we speculate that paeonol protected memory after ischemic stroke via reducing APP, BACE, and apoptosis. Supression the level of Bax and blocking the release of AIF into cytosol might participate in the anti-apoptosis providedby paeonol.

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