Effects of 2.45-GHz Electromagnetic Fields with a Wide Range of SARs on Micronucleus Formation in CHO-K1 Cells

There has been considerable discussion about the influence of high-frequency electromagnetic fields (HFEMF) on the human body. In particular, HFEMF used for mobile phones may be of great concern for human health. In order to investigate the properties of HFEMF, we have examined the effects of 2.45-GHz EMF on micronucleus (MN) formation in Chinese hamster ovary (CHO)-K1 cells. MN formation is induced by chromosomal breakage or inhibition of spindles during cell division and leads to cell damage. We also examined the influence of heat on MN formation, since HFEMF exposure causes a rise in temperature. CHO-K1 cells were exposed to HFEMF for 2 h at average specific absorption rates (SARs) of 5, 10, 20, 50, 100, and 200 W/kg, and the effects on these cells were compared with those in sham-exposed control cells. The cells were also treated with bleomycin alone as a positive control or with combined treatment of HFEMF exposure and bleomycin. Heat treatment was performed at temperatures of 37, 38, 39, 40, 41, and 42°C.The MN frequency in cells exposed to HFEMF at a SAR of lower than 50 W/kg did not differ from the sham-exposed controls, while those at SARs of 100 and 200 W/kg were significantly higher when compared with the sham-exposed controls. There was no apparent combined effect of HFEMF exposure and bleomycin treatment. On heat treatment at temperatures from 38–42°C, the MN frequency increased in a temperature-dependent manner. We also showed that an increase in SAR causes a rise in temperature and this may be connected to the increase in MN formation generated by exposure to HFEMF.

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NEPHROPROTECTIVE ACTIVITY OF ETHANOL EXTRACT OF CURCUMA MANGGA VAL. IN PARACETAMOL-INDUCED MALE MICE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s1.26585 ◽

2018 ◽

Vol 11 (13) ◽

pp. 126

Author(s):

Rosita Rosita ◽

Yuandani Yuandani ◽

Marianne Marianne

Keyword(s):

Creatinine Level ◽

Cell Damage ◽

Ethanol Extract ◽

Positive Control ◽

Negative Control ◽

Dependent Manner ◽

Male Mice ◽

Treatment Groups ◽

Level Measurement ◽

Nephroprotective Activity

Objective: This study aimed to evaluate nephroprotective activity of Curcuma mangga in paracetamol-induced male mice.Methods: Male mice were divided into several groups including normal control, negative, positive, and treatment groups. Treatment groups were orally administered with C. mangga extract at doses of 100, 200, and 400 mg/kg bw for 7 days. On day 7after 1 h of treatment, the mice were induced with paracetamol 1.05 g/kg bw. Serum creatinine level measurement and histopathotlogy study were performed at the end of experiment.Results: C. mangga extract was able to inhibit the increase of creatinine level and showed a significantly different from negative control (p<0.05) and did not different significantly from positive control (p>0.05). The result was supported by histopathology examination which did not show any cell damage. The nephroprotective effect of C. mangga was in a dose-dependent manner. C. mangga extract at dose of 400 mg/kg bw depicted the strongest nephroprotective effect.Conclusion: C. mangga extract was able to protect mice kidney induced by paracetamol.

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Substrate protection against inactivation of the mammalian polyamine-transport system by 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide

Biochemical Journal ◽

10.1042/bj3190021 ◽

1996 ◽

Vol 319 (1) ◽

pp. 21-26 ◽

Cited By ~ 10

Author(s):

Krikor TOROSSIAN ◽

Marie AUDETTE ◽

Richard POULIN

Keyword(s):

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Amino Acid Uptake ◽

Acid Uptake ◽

Dependent Manner ◽

Temperature Dependent ◽

Concentration Dependent Manner ◽

Ovary Cells ◽

Polyamine Transport ◽

Substrate Protection

Mammalian polyamine transporters have not thus far been biochemically characterized. Since essential carboxy groups in the polyamine carrier might participate in the transport process, the ability of two different carbodi-imides to affect [3H]spermidine uptake was assessed in Chinese hamster ovary cells. Both the hydrophobic 1,3-dicyclohexylcarbodi-imide (DCC) and the more polar 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide (EDC) irreversibly inhibited spermidine transport with EC50 values of 11±4 and 96±16 µM after 30 min at 22 °C respectively. Prior treatment with EDC in the absence of substrate decreased both the Vmax and Km for spermidine uptake in a time- and concentration-dependent manner. Spermidine-transport inactivation by EDC (1 mM) was temperature-dependent, with 60 and 90% inhibition observed after 10 min at 22 and 37 °C respectively. Spermine (10 µM) almost fully protected against spermidine-transport inactivation by EDC at 22 °C, and decreased the rate of inactivation at 37 °C by about 80%. Putrescine, spermidine and spermine were all effective in protecting against EDC-mediated inactivation of [3H]spermidine and [3H]putrescine uptake at 22 °C with EC50 values estimated at 10, 1 and less than 1 µM respectively. The nucleophile glycine ethyl ester (up to 50 mM) prevented the inhibition brought about by 1 mM EDC. Inhibition by 1 mM EDC was greater at pH 7.2 than at pH 5.8 (89±3 compared with 44±5%), whereas the converse was true for 100 µM DCC (81±3 compared with 92±5%). On the other hand, spermine did not protect against inactivation of spermidine uptake by DCC. Moreover, DCC, but not EDC, inhibited Na+-dependent amino acid uptake. The present data indicate that (i) EDC and DCC inhibit polyamine transport through distinct mechanisms, (ii) substrate binding occludes one or several carboxy groups lying in a polar environment of the carrier and (iii) these carboxyl residues might be activated by EDC to cross-link a neighbouring nucleophile side group, resulting in a conformation of the polyamine carrier which is inactive for transport.

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MAP6-F Is a Temperature Sensor That Directly Binds to and Protects Microtubules from Cold-induced Depolymerization

Journal of Biological Chemistry ◽

10.1074/jbc.m112.398339 ◽

2012 ◽

Vol 287 (42) ◽

pp. 35127-35138 ◽

Cited By ~ 27

Author(s):

Christian Delphin ◽

Denis Bouvier ◽

Maxime Seggio ◽

Emilie Couriol ◽

Yasmina Saoudi ◽

...

Keyword(s):

Conformational Changes ◽

Temperature Sensor ◽

Cold Sensitivity ◽

Dependent Manner ◽

Temperature Dependent ◽

Microtubule Network ◽

Wide Range ◽

In Cells

Microtubules are dynamic structures that present the peculiar characteristic to be ice-cold labile in vitro. In vivo, microtubules are protected from ice-cold induced depolymerization by the widely expressed MAP6/STOP family of proteins. However, the mechanism by which MAP6 stabilizes microtubules at 4 °C has not been identified. Moreover, the microtubule cold sensitivity and therefore the needs for microtubule stabilization in the wide range of temperatures between 4 and 37 °C are unknown. This is of importance as body temperatures of animals can drop during hibernation or torpor covering a large range of temperatures. Here, we show that in the absence of MAP6, microtubules in cells below 20 °C rapidly depolymerize in a temperature-dependent manner whereas they are stabilized in the presence of MAP6. We further show that in cells, MAP6-F binding to and stabilization of microtubules is temperature- dependent and very dynamic, suggesting a direct effect of the temperature on the formation of microtubule/MAP6 complex. We also demonstrate using purified proteins that MAP6-F binds directly to microtubules through its Mc domain. This binding is temperature-dependent and coincides with progressive conformational changes of the Mc domain as revealed by circular dichroism. Thus, MAP6 might serve as a temperature sensor adapting its conformation according to the temperature to maintain the cellular microtubule network in organisms exposed to temperature decrease.

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Neuroprotective Effects of Extracts from the Radix Curcuma aromatica on H2O2-induced Damage in PC12 Cells

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666181005121457 ◽

2018 ◽

Vol 21 (8) ◽

pp. 571-582 ◽

Cited By ~ 1

Author(s):

Juxiang Liu ◽

Lianli Zhang ◽

Dan Liu ◽

Baocai Li ◽

Mi Zhang

Keyword(s):

Oxidative Stress ◽

Pc12 Cells ◽

Caspase 3 ◽

Cell Damage ◽

Positive Control ◽

Neuroprotective Activity ◽

Antioxidant Enzyme Activities ◽

Morphologic Change ◽

Neuroprotective Effects ◽

Etoh Extract

Aim & Objectives: Curcuminoids are characteristic constituents in Curcuma, displaying obviously neuroprotective activities against oxidative stress. As one of the Traditional Chinese Medicines from Curcuma, the radix of Curcuma aromatica is also rich in those chemicals, but its neuroprotective activity and mechanism remain unknown. The aim of the current study is to evaluate the neuroprotective effects of extracts from the radix of C. aromatica (ECAs) on H2O2-damaged PC12 cells. Material and Methods: The model of oxidative stress damage was established by treatment of 400 µM H2O2 on PC12 to induce cell damage. After the treatment of ECWs for 24 h, the cell viability, LDH, SOD, CAT and GSH were measured to evaluate the neuroprotection of ECAs on that model. The potential action mechanism was studied by measurement of level of ROS, cell apoptosis rate, mitochondrial membrane potential (MMP), morphologic change, the intracellular Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3. Additionally, the constituents from tested extracts were analyzed by HPLC-DAD-Q-TOF-MS method. Results: Compared with a positive control, Vitamin E, 10 µg/ml of 95% EtOH extract (HCECA) and 75% EtOH extract (MCECA) can markedly increase the rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT, increase the levels of GSH, decrease LDH release and the level of ROS, attenuate the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression, and improve the change of cell morphology. The chemical analysis showed that diarylheptanoids and sesquiterpenoids are the major chemicals in tested extracts and the former were richer in HCECA and MCECA than others. Conclusions: These findings indicated that the effects of HCECA and MCECA on inhibiting the cells damage induced by H2O2 in PC12 are better than other extracts from the radix of C. aromatica, and the active constituents with neuroprotective effects consisting in those two active extracts are diarylheptanoids.

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Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180412114750 ◽

2019 ◽

Vol 18 (10) ◽

pp. 1448-1456 ◽

Cited By ~ 3

Author(s):

Bahareh Movafegh ◽

Razieh Jalal ◽

Zobeideh Mohammadi ◽

Seyyede A. Aldaghi

Keyword(s):

Cell Death ◽

Cellular Uptake ◽

Combined Treatment ◽

Annexin V ◽

Cell Penetrating Peptides ◽

Short Exposure ◽

Dependent Manner ◽

Du145 Cells ◽

Induced Apoptosis ◽

Resistance To Doxorubicin

Objective: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell-penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. Methods: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide- acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicininduced cell death. Results: Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24h combined treatment of cells with doxorubicin (0.5 µM) and poly-L-arginine (1 µg ml-1) caused a small increase in doxorubicin-induced apoptosis and significantly elevated necrosis in DU145 cells as compared to each agent alone. Conclusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferationinducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis.

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Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro

Molecules ◽

10.3390/molecules25184293 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4293

Author(s):

Zhen-Wang Li ◽

Chun-Yan Zhong ◽

Xiao-Ran Wang ◽

Shi-Nian Li ◽

Chun-Yuan Pan ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Cells ◽

Antiproliferative Activity ◽

Antitumor Agent ◽

Positive Control ◽

Selectivity Index ◽

Time Dependent ◽

Potential Candidate ◽

Dependent Manner

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

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Dual Electrochemical Treatments to Improve Properties of Ti6Al4V Alloy

Materials ◽

10.3390/ma13112479 ◽

2020 ◽

Vol 13 (11) ◽

pp. 2479

Author(s):

Stefano Rossi ◽

Luciana Volgare ◽

Carine Perrin-Pellegrino ◽

Carine Chassigneux ◽

Erick Dousset ◽

...

Keyword(s):

Heat Treatment ◽

Combined Treatment ◽

Amorphous Film ◽

Amorphous Layer ◽

Good Alternative ◽

Surface Treatments ◽

Ex Situ ◽

X Ray Diffraction ◽

Transmission Electron ◽

Fluid Environment

Surface treatments are considered as a good alternative to increase biocompatibility and the lifetime of Ti-based alloys used for implants in the human body. The present research reports the comparison of bare and modified Ti6Al4V substrates on hydrophilicity and corrosion resistance properties in body fluid environment at 37 °C. Several surface treatments were conducted separately to obtain either a porous oxide layer using nanostructuration (N) in ethylene glycol containing fluoride solution, or bulk oxide thin films through heat treatment at 450 °C for 3 h (HT), or electrochemical oxidation at 1 V for 3 h (EO), as well as combined treatments (N-HT and N-EO). In-situ X-ray diffraction and ex-situ transmission electron microscopy have shown that heat treatment gave first rise to the formation of a 30 nm thick amorphous layer which crystallized in rutile around 620 °C. Electrochemical oxidations gave rise to a 10 nm thick amorphous film on the top of the surface (EO) or below the amorphous nanotube layer (N-EO). Dual treated samples presented similar results with a more stable behavior for N-EO. Finally, for both corrosion and hydrophilicity points of view, the new combined treatment to get a total amorphous N-EO sample seems to be the best and even better than the partially crystallized N-HT sample.

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A Bacterial Tower of Babel: Quorum-Sensing Signaling Diversity and Its Evolution

Annual Review of Microbiology ◽

10.1146/annurev-micro-012220-063740 ◽

2020 ◽

Vol 74 (1) ◽

pp. 587-606 ◽

Cited By ~ 1

Author(s):

Nitzan Aframian ◽

Avigdor Eldar

Keyword(s):

Quorum Sensing ◽

Social Interactions ◽

Signal Molecules ◽

Allelic Polymorphism ◽

Dependent Manner ◽

Tower Of Babel ◽

Cognate Receptor ◽

Wide Range ◽

Family Code ◽

Bacterial Groups

Quorum sensing is a process in which bacteria secrete and sense a diffusible molecule, thereby enabling bacterial groups to coordinate their behavior in a density-dependent manner. Quorum sensing has evolved multiple times independently, utilizing different molecular pathways and signaling molecules. A common theme among many quorum-sensing families is their wide range of signaling diversity—different variants within a family code for different signal molecules with a cognate receptor specific to each variant. This pattern of vast allelic polymorphism raises several questions—How do different signaling variants interact with one another? How is this diversity maintained? And how did it come to exist in the first place? Here we argue that social interactions between signaling variants can explain the emergence and persistence of signaling diversity throughout evolution. Finally, we extend the discussion to include cases where multiple diverse systems work in concert in a single bacterium.

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Growth Promotion or Osmotic Stress Response: How SNF1-Related Protein Kinase 2 (SnRK2) Kinases Are Activated and Manage Intracellular Signaling in Plants

Plants ◽

10.3390/plants10071443 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1443

Author(s):

Yoshiaki Kamiyama ◽

Sotaro Katagiri ◽

Taishi Umezawa

Keyword(s):

Protein Kinase ◽

Plant Growth ◽

Osmotic Stress ◽

Protein Function ◽

Intracellular Signaling ◽

Growth Promotion ◽

Research Field ◽

Dependent Manner ◽

Related Protein ◽

Wide Range

Reversible phosphorylation is a major mechanism for regulating protein function and controls a wide range of cellular functions including responses to external stimuli. The plant-specific SNF1-related protein kinase 2s (SnRK2s) function as central regulators of plant growth and development, as well as tolerance to multiple abiotic stresses. Although the activity of SnRK2s is tightly regulated in a phytohormone abscisic acid (ABA)-dependent manner, recent investigations have revealed that SnRK2s can be activated by group B Raf-like protein kinases independently of ABA. Furthermore, evidence is accumulating that SnRK2s modulate plant growth through regulation of target of rapamycin (TOR) signaling. Here, we summarize recent advances in knowledge of how SnRK2s mediate plant growth and osmotic stress signaling and discuss future challenges in this research field.

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CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22105394 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5394

Author(s):

Tomas Lidak ◽

Nikol Baloghova ◽

Vladimir Korinek ◽

Radislav Sedlacek ◽

Jana Balounova ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Ubiquitin Ligase ◽

Cell Activation ◽

Rna Helicase ◽

Dependent Manner ◽

Amino Acid Residues ◽

Risc Complex ◽

Wide Range

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

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