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1.
Int J Cancer ; 145(5): 1395-1407, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30828790

RESUMO

Metastasis of colorectal cancer (CRC) is the leading cause of CRC-associated mortality. Angiogenin (ANG), a member of the ribonuclease A superfamily, not only activates endothelial cells to induce tumor angiogenesis, but also targets tumor cells to promote cell survival, proliferation and/or migration. However, its clinical significance and underlying mechanism in CRC metastasis are still largely unknown. Here, we reported that ANG was upregulated in CRC tissues and associated with metastasis in CRC patients. We then revealed that ANG enhanced CRC growth and metastasis in both in vitro and in vivo systems. Intriguingly, we characterized a bunch of tRNA-derived stress-induced small RNAs (tiRNAs), produced through ANG cleavage, that was enriched in both CRC tumor tissues and highly metastatic cells, and functioned in ANG-promoted CRC metastasis. Moreover, higher level of a 5'-tiRNA from mature tRNA-Val (5'-tiRNA-Val) was observed in CRC patients and was correlated with tumor metastasis. Taken together, we propose that a novel ANG-tiRNAs-cell migration and invasion regulatory axis promotes CRC metastasis, which might be of potential target for CRC diagnosis and treatment.

2.
Cell Death Dis ; 10(2): 127, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755584

RESUMO

Silica nanoparticles (SiNPs) have been reported to induce pulmonary fibrosis (PF) with an unknown mechanism. Recently, the activation of autophagy, a lysosome-dependent cell degradation pathway, by SiNPs has been identified in alveolar epithelial cells (AECs). However, the underlying mechanism and the relevance of SiNPs-induced autophagy to the development of PF remain elusive. Here, we report that autophagy dysfunction and subsequent apoptosis in AECs are involved in SiNPs-induced PF. SiNPs engulfed by AECs enhance autophagosome accumulation and apoptosis both in vivo and in vitro. Mechanically, SiNPs block autophagy flux through impairing lysosomal degradation via acidification inhibition. Lysosomal reacidification by cyclic-3',5'-adenosine monophosphate (cAMP) significantly enhances autophagic degradation and attenuate apoptosis. Importantly, enhancement of autophagic degradation by rapamycin protects AECs from apoptosis and attenuates SiNPs-induced PF in the mouse model. Altogether, our data demonstrate a repressive effect of SiNPs on lysosomal acidification, contributing to the decreased autophagic degradation in AECs, thus leading to apoptosis and subsequent PF. These findings may provide an improved understanding of SiNPs-induced PF and molecular targets to antagonize it.

3.
Angiogenesis ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30465119

RESUMO

The miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models. Particularly, the effect of miR-141 in vascular endothelial cells has not been defined. In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis. Additional mechanistic studies showed that miR-141 suppresses angiogenesis through multiple targets, including NRP1, GAB1, CXCL12ß, TGFß2, and GATA6, and bioinformatics analysis indicated that miR-141 and its targets comprise a powerful and precise regulatory network to modulate angiogenesis. Taken together, these data not only demonstrate an anti-angiogenic effect of miR-141, further strengthening the critical role of miR-200 family in the process of angiogenesis, but also provides a valuable cancer therapeutic target to control both angiogenesis and EMT, two essential steps in tumor growth and metastasis.

4.
Bioelectromagnetics ; 39(6): 476-484, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30091795

RESUMO

Extremely low frequency magnetic field (ELF-MF) has been classified as a possible carcinogen to humans by the International Agency for Research on Cancer [2002]. However, debate on the genotoxic effects of ELF-MF has continued due to lack of sufficient experimental evidence. Ataxia telangiectasia mutated (ATM) plays a central role in DNA damage repair; its deficiency can result in cellular sensitivity to DNA-damaging agents. To evaluate the genotoxicity of ELF-MF, we investigated the effects of 50 Hz MF on DNA damage in ATM-proficient (Atm+/+ ) mouse embryonic fibroblasts (MEFs) and ATM-deficient (Atm-/- ) MEFs, a radiosensitive cell line. Results showed no significant difference in average number of γH2AX foci per cell (9.37 ± 0.44 vs. 9.08 ± 0.28, P = 0.58) or percentage of γH2AX foci positive cells (49.22 ± 1.86% vs. 49.74 ± 1.44%, P = 0.83) between sham and exposure groups when Atm+/+ MEFs were exposed to 50 Hz MF at 2.0 mT for 15 min. Extending exposure duration to 1 or 24 h did not significantly change γH2AX foci formation in Atm+/+ MEFs. Similarly, the exposure did not significantly affect γH2AX foci formation in Atm-/- MEFs. Furthermore, 50 Hz MF exposure also did not significantly influence DNA fragmentation, cell viability, or cell cycle progression in either cell types. In conclusion, exposure to 50 Hz MF did not induce significant DNA damage in either Atm+/+ or Atm-/- MEFs under the reported experimental conditions. Bioelectromagnetics. 39:476-484, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Campos Eletromagnéticos , Fibroblastos/fisiologia , Animais , Proteínas Mutadas de Ataxia Telangiectasia/deficiência , Proteínas Mutadas de Ataxia Telangiectasia/genética , Ciclo Celular , Linhagem Celular , Sobrevivência Celular , Ensaio Cometa , Fragmentação do DNA , Campos Eletromagnéticos/efeitos adversos , Fibroblastos/patologia , Imunofluorescência , Predisposição Genética para Doença , Histonas/metabolismo , Camundongos , Camundongos Knockout
5.
Dis Markers ; 2018: 1984718, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736193

RESUMO

Background: Angiogenin (ANG) is a multifunctional angiogenic protein that participates in both normal development and diseases. Abnormal serum ANG levels are commonly reported in various diseases. However, whether ANG can serve as a diagnostic or prognostic marker for different diseases remains a matter of debate. Methods: Here, we performed a systematic review and meta-analysis of the literature utilizing PubMed, Web of Science, and Scopus search engines to identify all publications comparing plasma or serum ANG levels between patients with different diseases and healthy controls, as were studies evaluating circulating ANG levels in healthy populations, pregnant women, or other demographic populations. Results: This study demonstrated that the serum ANG concentration in healthy populations was 336.14 ± 142.83 ng/ml and remained relatively stable in different populations and regions. We noted no significant differences in serum ANG levels between patients and healthy controls, except in cases in which patients suffered from cancer or cardiovascular diseases. The serum ANG concentrations were significantly higher in patients who developed colorectal cancer, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes, and heart failure than those in healthy controls. Conclusion: ANG has the potential of being a serum biomarker for cancers and cardiovascular diseases.


Assuntos
Angiotensinas/sangue , Neoplasias Colorretais/sangue , Insuficiência Cardíaca/sangue , Leucemia Mieloide/sangue , Mieloma Múltiplo/sangue , Síndromes Mielodisplásicas/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino
6.
Genes (Basel) ; 9(5)2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29748504

RESUMO

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

7.
Int J Radiat Biol ; 94(3): 295-305, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29368975

RESUMO

PURPOSE: To systematically evaluate the effects of 1800 MHz radiofrequency electromagnetic fields (RF-EMF) exposure on DNA damage and cellular functions in primary cultured neurogenic cells. MATERIALS AND METHODS: The primary cultured astrocytes, microglia and cortical neurons were exposed to RF-EMF at a SAR of 4.0 W/kg. The DNA damage was evaluated by γH2AX foci formation assay. The secretions of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) in astrocytes and microglia, microglial phagocytic activity and neuronal development were examined by enzyme-linked immunosorbent assay, phagocytosis assay and immunofluorescent staining on microtubule-associated protein tau, microtubule-associated protein 2, postsynaptic density 95 and gephyrin, respectively. RESULTS: RF-EMF exposure did not significantly induce γH2AX foci formation in three primary cultured neurogenic cells. Furthermore, RF-EMF exposure did not significantly affect the secretion of cytokines in astrocytes and microglia, and the morphological indicators of dendrites or synapses of cortical neurons. However, the exposure significantly reduced the phagocytic activity of microglia and inhibited the axon branch length and branch number of cortical neurons. CONCLUSIONS: Our data demonstrated that exposure to RF-EMF did not elicit DNA damage but inhibited the phagocytic ability of microglia and the axon branch length and branch number of cortical neurons.

8.
Gene ; 639: 111-116, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29020616

RESUMO

Follistatin (FST), a single-chain glycosylated protein, is expressed in various tissues. The essential biological function of FST is binding and neutralizing transforming growth factor ß (TGF-ß) superfamily, including activin, myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that FST also serves as a stress responsive protein, which plays a protective role under a variety of stresses. In most cases, FST performs the protective function through its neutralization of TGF-ß superfamily. However, under certain circumstances, FST translocates into the nucleus to maintain cellular homeostasis independent of its extracellular antagonism activity. This review provides integrated insight into the most recent advances in understanding the role of FST under various stresses, and the clinical implications corresponding to these findings and discusses the mechanisms to be further studied.


Assuntos
Folistatina/fisiologia , Estresse Fisiológico/fisiologia , Folistatina/genética , Folistatina/metabolismo , Humanos , Processamento de Proteína Pós-Traducional , Processamento Pós-Transcricional do RNA
9.
Mol Neurobiol ; 55(2): 1338-1351, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28127696

RESUMO

Gene defects have been recognized as prominent factors in the etiology and pathogenesis of neurodegeneration. Among 60 neurodegeneration-related mutations in progranulin (PGRN), a mutation in PGRN gene exon 1 introduces a charged amino acid in the hydrophobic core of its signal peptide at residue 9 (named PGRN A9D) and results in incorrect cytoplasmic sorting. However, the pathogenesis of this mutation remains elusive. To address this issue, we first examined the subcellular distribution of PGRN A9D in human neuronal-like cells (SH-SY5Y). The results showed that PGRN A9D accumulated in cytosolic stress granules. Interestingly, this mis-sorting associated with a cellular redistribution of angiogenin (ANG), a stress-response factor and neurodegenerative disease-related protein, from nucleus to cytoplasmic stress granules, and there existed protein interaction between PGRN A9D and ANG. Further study revealed that the stress granule localization of PGRN A9D was dependent on ANG. Functionally, PGRN A9D abolished the nuclear ANG-mediated biological roles; on the other hand, the relocation of ANG to stress granules activated its cytoprotective stress-response program by cleaving transfer RNAs (tRNAs) to tiRNAs (tRNA-derived, stress-induced small RNAs), thus promoting PGRN A9D cell survival. Taken together, we hypothesize that PGRN A9D leads to the retention of ANG in the cytoplasm to protect cells from PGRN A9D-induced apoptosis, implying that PGRN and ANG act in concert to regulate the progress of neurodegenerative disease.

10.
Cell Mol Life Sci ; 74(20): 3841-3850, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28612218

RESUMO

When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique-Particle Image Velocimetry (PIV)-we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A particle-based compass (PBC) model suggests cellular interplay (which depends on cell-cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.


Assuntos
Cálcio/metabolismo , Comunicação Celular , Movimento Celular , Epitélio Anterior/citologia , Materiais Biocompatíveis/química , Contagem de Células , Linhagem Celular , Dimetilpolisiloxanos/química , Epitélio Anterior/metabolismo , Humanos , Modelos Biológicos , Cicatrização
11.
J Radiat Res ; 58(4): 474-486, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28369556

RESUMO

Epidemiological studies have indicated a possible association between extremely low-frequency magnetic field (ELF-MF) exposure and the risk of nervous system diseases. However, laboratory studies have not provided consistent results for clarifying this association, despite many years of studies. In this study, we have systematically investigated the effects of 50 Hz MF exposure on DNA damage and cellular functions in both neurogenic tumor cell lines (U251, A172, SH-SY5Y) and primary cultured neurogenic cells from rats (astrocytes, microglia, cortical neurons). The results showed that exposure to a 50 Hz MF at 2.0 mT for up to 24 h did not influence γH2AX foci formation (an early marker of DNA double-strand breaks) in any of six different neurogenic cells. Exposure to a 50 Hz MF did not affect cell cycle progression, cell proliferation or cell viability in neurogenic tumor U251, A172 or SH-SY5Y cells. Furthermore, the MF exposure for 24 h did not significantly affect the secretion of cytokines (TNF-α, IL-6 or IL-1ß) in astrocytes or microglia, or the phagocytic activity of microglia. In addition, MF exposure for 1 h per day did not significantly influence expression levels of microtubule-associated protein tau, microtubule-associated protein 2, postsynaptic density 95 or gephyrin in cortical neurons, indicating an absence of effects of MF exposure on the development of cortical neurons. In conclusion, our data suggest that exposure to a 50 Hz MF at 2.0 mT did not elicit DNA damage effects or abnormal cellular functions in the neurogenic cells studied.


Assuntos
Dano ao DNA , Campos Magnéticos , Neurônios/patologia , Neurônios/efeitos da radiação , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Astrócitos/efeitos da radiação , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Forma Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Citocinas/metabolismo , Histonas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Microglia/metabolismo , Microglia/efeitos da radiação , Microesferas , Neurônios/metabolismo , Fagocitose/efeitos da radiação , Ratos Sprague-Dawley
12.
Bioelectromagnetics ; 38(3): 175-185, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28026047

RESUMO

Despite many years of studies, the debate on genotoxic effects of radiofrequency electromagnetic fields (RF-EMF) continues. To systematically evaluate genotoxicity of RF-EMF, this study examined effects of RF-EMF on DNA damage and cellular behavior in different neurogenic cells. Neurogenic A172, U251, and SH-SY5Y cells were intermittently (5 min on/10 min off) exposed to 1800 MHz RF-EMF at an average specific absorption rate (SAR) of 4.0 W/kg for 1, 6, or 24 h. DNA damage was evaluated by quantification of γH2AX foci, an early marker of DNA double-strand breaks. Cell cycle progression, cell proliferation, and cell viability were examined by flow cytometry, hemocytometer, and cell counting kit-8 assay, respectively. Results showed that exposure to RF-EMF at an SAR of 4.0 W/kg neither significantly induced γH2AX foci formation in A172, U251, or SH-SY5Y cells, nor resulted in abnormal cell cycle progression, cell proliferation, or cell viability. Furthermore, prolonged incubation of these cells for up to 48 h after exposure did not significantly affect cellular behavior. Our data suggest that 1800 MHz RF-EMF exposure at 4.0 W/kg is unlikely to elicit DNA damage or abnormal cellular behaviors in neurogenic cells. Bioelectromagnetics. 38:175-185, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Dano ao DNA , Campos Eletromagnéticos/efeitos adversos , Glioblastoma/patologia , Neuroblastoma/patologia , 4-Nitroquinolina-1-Óxido/toxicidade , Ciclo Celular , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Dano ao DNA/efeitos dos fármacos , Glioblastoma/genética , Histonas/genética , Humanos , Testes de Mutagenicidade/instrumentação , Testes de Mutagenicidade/métodos , Neuroblastoma/genética , Ondas de Rádio
13.
Sci Rep ; 6: 37423, 2016 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-27857169

RESUMO

Radiofrequency electromagnetic fields (RF-EMFs) have been classified by the International Agency for Research on Cancer as possible carcinogens to humans; however, this conclusion is based on limited epidemiological findings and lacks solid support from experimental studies. In particular, there are no consistent data regarding the genotoxicity of RF-EMFs. Ataxia telangiectasia mutated (ATM) is recognised as a chief guardian of genomic stability. To address the debate on whether RF-EMFs are genotoxic, we compared the effects of 1,800 MHz RF-EMF exposure on genomic DNA in mouse embryonic fibroblasts (MEFs) with proficient (Atm+/+) or deficient (Atm-/-) ATM. In Atm+/+ MEFs, RF-EMF exposure for 1 h at an average special absorption rate of 4.0 W/kg induced significant DNA single-strand breaks (SSBs) and activated the SSB repair mechanism. This effect reduced the DNA damage to less than that of the background level after 36 hours of exposure. In the Atm-/- MEFs, the same RF-EMF exposure for 12 h induced both SSBs and double-strand breaks and activated the two repair processes, which also reduced the DNA damage to less than the control level after prolonged exposure. The observed phenomenon is similar to the hormesis of a toxic substance at a low dose. To the best of our knowledge, this study is the first to report a hormesis-like effect of an RF-EMF.


Assuntos
Telefone Celular , Campos Eletromagnéticos/efeitos adversos , Ondas de Rádio/efeitos adversos , Animais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Quebras de DNA/efeitos da radiação , Dano ao DNA/efeitos da radiação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Técnicas de Inativação de Genes , Hormese/efeitos da radiação , Humanos , Camundongos
14.
Sci Total Environ ; 571: 452-60, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27396316

RESUMO

The effects of antimony (Sb) exposure on mortalities, cancers and cardiovascular diseases were controversial in occupational workers, and the evidence from the general population is limited. The objective of this study is to investigate the relationships between Sb exposure and specific health events in the general population. Totally, 7781 participants aged ≥20years were selected from the National Health and Nutrition Examination Survey (NHANES) 1999-2010 and were followed for an average of 6.04years. The Cox and logistic regression models were applied to evaluate the effects of urinary Sb (U-Sb) levels on the risks of all-cause and cause-specific mortalities, and the likelihoods of self-reported cancers and heart diseases, respectively. When setting quartile 1 of U-Sb levels as reference, the hazard ratios (HRs) [95% confidence intervals (CIs)] of the quartile 2 through 4 for all-cause mortality were 1.21 (0.84, 1.74), 1.49 (1.08, 2.04) and 1.66 (1.20, 2.28). The HR of quartile 3 of U-Sb levels for heart disease mortality was 2.18 (1.24, 3.86). Furthermore, increased odds ratios (ORs) from quartile 2 to 4 were 1.69 (1.05, 2.74), 1.42 (0.79, 2.55) and 2.11 (1.26, 3.55) for self-reported congestive heart failure, and 1.37 (0.95, 1.99), 1.96 (1.37, 2.82) and 1.81 (1.16, 2.83) for heart attack. Elevated U-Sb levels were not significantly related to mortality of malignant neoplasms, and self-reported cancers. The data demonstrated associations of increased U-Sb levels with all-cause and heart diseases mortalities, and prevalent congestive heart failure and heart attack, suggesting public concerns on the health hazards of Sb exposure in the general population.


Assuntos
Antimônio/urina , Cardiopatias/epidemiologia , Neoplasias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Neoplasias/mortalidade , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
15.
J Cell Sci ; 129(16): 3104-14, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27358480

RESUMO

Excitatory amino acid transporter type 3 (EAAT3, also known as SLC1A1) is a high-affinity, Na(+)-dependent glutamate carrier that localizes primarily within the cell and at the apical plasma membrane. Although previous studies have reported proteins and sequence regions involved in EAAT3 trafficking, the detailed molecular mechanism by which EAAT3 is distributed to the correct location still remains elusive. Here, we identify that the YVNGGF sequence in the C-terminus of EAAT3 is responsible for its intracellular localization and apical sorting in rat hepatoma cells CRL1601 and Madin-Darby canine kidney (MDCK) cells, respectively. We further demonstrate that Numb, a clathrin adaptor protein, directly binds the YVNGGF motif and regulates the localization of EAAT3. Mutation of Y503, N505 and F508 within the YVNGGF motif to alanine residues or silencing Numb by use of small interfering RNA (siRNA) results in the aberrant localization of EAAT3. Moreover, both Numb and the YVNGGF motif mediate EAAT3 endocytosis in CRL1601 cells. In summary, our study suggests that Numb is a pivotal adaptor protein that mediates the subcellular localization of EAAT3 through binding the YxNxxF (where x stands for any amino acid) motif.


Assuntos
Transportador 3 de Aminoácido Excitatório/química , Transportador 3 de Aminoácido Excitatório/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Motivos de Aminoácidos , Animais , Cães , Endocitose , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Mutação/genética , Ligação Proteica , Transporte Proteico , Ratos , Relação Estrutura-Atividade , Frações Subcelulares/metabolismo
16.
Int J Biochem Cell Biol ; 77(Pt A): 72-79, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27177844

RESUMO

As electromagnetic field (EMF) is commonly encountered within our daily lives, the biological effects of EMF are of great concern. Autophagy is a key process for maintaining cellular homeostasis, and it can also reveal cellular responses to environmental stimuli. In this study, we aim to investigate the biological effects of a 50Hz-sinusoidal electromagnetic field on autophagy and we identified its mechanism of action in Chinese Hamster Lung (CHL) cells. CHL cells were exposed to a 50Hz sinusoidal EMF at 0.4mT for 30min or 24h. In this study, we found that a 0.4mT EMF resulted in: (i) an increase in LC3-II expression and increased autophagosome formation; (ii) no significant difference in the incidence of γH2AX foci between the sham and exposure groups; (iii) reorganized actin filaments and increased pseudopodial extensions without promoting cell migration; and (iv) enhanced cell apoptosis when autophagy was blocked by Bafilomycin A1. These results implied that DNA damage was not directly involved in the autophagy induced by a 0.4mT 50Hz EMF. In addition, an EMF induced autophagy balanced the cellular homeostasis to protect the cells from severe adverse biological consequences.


Assuntos
Autofagia/efeitos da radiação , Dano ao DNA , Campos Eletromagnéticos , Actinas/metabolismo , Animais , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Cricetinae , Relação Dose-Resposta à Radiação
17.
Sci Rep ; 6: 21133, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26878911

RESUMO

Silica nanoparticles (SiO2 NPs) cause oxidative stress in respiratory system. Meanwhile, human cells launch adaptive responses to overcome SiO2 NP toxicity. However, besides a few examples, the regulation of SiO2 NP-responsive proteins and their functions in SiO2 NP response remain largely unknown. In this study, we demonstrated that SiO2 NP induced the expression of follistatin (FST), a stress responsive gene, in mouse lung tissue as well as in human lung epithelial cells (A549). The levels of Ac-H3(K9/18) and H3K4me2, two active gene markers, at FST promoter region were significantly increased during SiO2 NP treatment. The induction of FST transcription was mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2), as evidenced by the decreased FST expression in Nrf2-deficient cells and the direct binding of Nrf2 to FST promoter region. Down-regulation of FST promoted SiO2 NP-induced apoptosis both in cultured cells and in mouse lung tissue. Furthermore, knockdown of FST increased while overexpression of FST decreased the expression level of NADPH oxidase 1 (NOX1) and NOX5 as well as the production of cellular reactive oxygen species (ROS). Taken together, these findings demonstrated a protective role of FST in SiO2 NP-induced oxidative stress and shed light on the interaction between SiO2 NPs and biological systems.


Assuntos
Células Epiteliais Alveolares/metabolismo , Folistatina/genética , Fator 2 Relacionado a NF-E2/metabolismo , Nanopartículas , Estresse Oxidativo , Dióxido de Silício , Ativação Transcricional , Animais , Apoptose/genética , Linhagem Celular , Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , NADPH Oxidase 1 , NADPH Oxidase 5 , NADPH Oxidases/genética , Nanopartículas/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/efeitos adversos
18.
Oncol Lett ; 11(1): 731-734, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870275

RESUMO

α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation of common adenocarcinoma cells, reverting them to a cancer stem cell state and producing AFP or hepatoid differentiation. Consequently, therapy targeted to the HGF/c-Met signaling pathway may potentially be effective for the treatment of AFP-producing colorectal adenocarcinoma.

19.
Environ Sci Pollut Res Int ; 23(3): 2495-504, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26423285

RESUMO

This study aimed to evaluate the effects of electromagnetic fields (EMF) exposure on levels of serum lipids in workers of an electric power plant. A cross-sectional study was carried out in an electric power plant in Zhejiang province, China, from August to September 2011. All participants were divided into two groups with high occupational EMF exposure and low occupational EMF exposure. The occupational EMF exposure included radiofrequency EMF and extremely low-frequency EMF. Occupational EMF exposure was associated with an increased level of low-density lipoprotein cholesterol (LDL-c; ß = 0.17 mmol/L, P = 0.022). High EMF exposure group with longer employment duration, longer daily EMF exposure duration, and more mobile phone or electric fee per month had significantly higher levels of total cholesterol, LDL-c, or triglyceride than the corresponding reference group. However, significantly decreased level of high-density lipoprotein cholesterol was only observed in high EMF exposure group with more mobile phone fee per month. Similar results were also found in 544 participants with available data of serum lipids in 2010. The findings showed that chronic EMF exposure was associated with the change of serum lipid levels. EMF exposure might modulate the process of lipid metabolism.


Assuntos
Campos Eletromagnéticos , Lipídeos/sangue , Exposição Ocupacional , Centrais Elétricas , Telefone Celular , China , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Ondas de Rádio
20.
Int Arch Occup Environ Health ; 89(1): 33-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25808749

RESUMO

PURPOSE: The potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant. METHODS: Seventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-κB, heat-shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay. RESULTS: EMF exposure group had statistically significantly lower levels of testosterone (ß = -0.3 nmol/L, P = 0.015), testosterone/estradiol (T/E2) ratio (ß = -15.6, P = 0.037), and NF-κB (ß = -20.8 ng/L, P = 0.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found. CONCLUSIONS: The findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Exposição Ocupacional/análise , Centrais Elétricas , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Telefone Celular/estatística & dados numéricos , Estudos Transversais , Emprego/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática , Estradiol/sangue , Proteínas de Choque Térmico HSP27/sangue , Proteínas de Choque Térmico HSP70/sangue , Humanos , Masculino , Melatonina/sangue , Pessoa de Meia-Idade , Oxigenases de Função Mista/sangue , NF-kappa B/sangue , Proteínas Proto-Oncogênicas/sangue , Testosterona/sangue , Fatores de Tempo , Adulto Jovem
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