A component of gamma-radiation-induced cell death in E. coli is programmed and interlinked with activation of caspase-3 and SOS response

2013 ◽  
Vol 195 (8) ◽  
pp. 545-557 ◽  
Author(s):  
Surbhi Wadhawan ◽  
Satyendra Gautam ◽  
Arun Sharma
Keyword(s):  
Cell Death ◽  
Gamma Radiation ◽  
Caspase 3 ◽  
Sos Response ◽  
E Coli ◽  
Radiation Induced

N-Acetyl-tryptophan glucoside (NATG) protects J774A.1 murine macrophages against gamma radiation-induced cell death by modulating oxidative stress

2018 ◽  
Vol 447 (1-2) ◽  
pp. 9-19 ◽  
Author(s):  
Poonam Malhotra ◽  
Ashutosh K. Gupta ◽  
Darshana Singh ◽  
Saurabh Mishra ◽  
Shravan K. Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Gamma Radiation ◽  
Murine Macrophages ◽  
Radiation Induced

scholarly journals Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

2016 ◽  
Vol 38 (2) ◽  
pp. 786-800 ◽  
Author(s):  
Mona Samy Guida ◽  
Ali Abd El-Aal ◽  
Yehya Kafafy ◽  
Safwat Farid Salama ◽  
Badr Mohamed Badr ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Gamma Radiation ◽  
Inflammatory Cytokine ◽  
Caspase 3 ◽  
Flow Cytometry Analysis ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Radiation Induced ◽  
Gamma Irradiated

Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4+ and CD8+ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.

scholarly journals Consequences of Lethal-Whole-Body Gamma Radiation and Possible Ameliorative Role of Melatonin

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ehsan Mihandoost ◽  
Alireza Shirazi ◽  
Seied Rabie Mahdavi ◽  
Akbar Aliasgharzadeh
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Gamma Radiation ◽  
Immune Suppression ◽  
Caspase 3 ◽  
Body Weight Loss ◽  
Whole Body ◽  
Radiation Induced ◽  
Effects Of Radiation

Gamma radiation induces the generation of free radicals, leading to serious cellular damages in biological systems. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the deleterious effects of radiation. Melatonin synergistically acts as an immune-stimulator and antioxidant. We investigated the possible radioprotective role of melatonin (100 mg/kg i.p.) against lethal-whole-body radiation- (10 Gy) induced sickness, body weight loss, and mortality in rats. Results of the present study suggest that exposure to lethal-whole-body radiation incurred mortality, body weight loss, and apoptosis and it also depleted the immunity and the antioxidant status of the rats. Our results show that melatonin pretreatment provides protection against radiation induced mortality, oxidative stress, and immune-suppression. The melatonin pretreated irradiated rats showed less change in body weight as compared to radiation only group. On the other hand, melatonin appeared to have another radioprotective role, suggesting that melatonin may reduce apoptosis through a caspase-3-mediated pathway by blocking caspase-3 activity.

Drp1 Activation Overcomes Diffuse Large B-Cell Lymphoma Cells Radioresistance

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5121-5121 ◽  
Author(s):  
Qingsong Pang ◽  
Ningbo Liu ◽  
Fengting Liu ◽  
Samir Agrawal ◽  
Ping Wang
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Parp Cleavage ◽  
Mitochondrial Fragmentation ◽  
Serine Kinase ◽  
Large B Cell Lymphoma ◽  
Radiation Induced ◽  
Large B Cell

Abstract Abstract 5121 Mitochondria undergo fusion and fission in response to physiological or pathological changes. Mitochondrial fusion is regulated by mitofusin-1 and 2 (MFN-1/2) and optic atrophy 1(OPA-1), whereas, mitochondrial fission (or fragmentation) is controlled by a Dynamin-related protein 1 (Drp1). Drp1 activation is triggered by dephosphorylation of Drp1 on its serine 637 site. Recent studies demonstrated that Drp1 activation plays an important role in mitochondrial fragmentation-induced cell death. The phosphorylation of Drp1 by serine kinase inhibits its GTPase activity and prevents mitochondrial fragmentation. Inhibition of Drp1 activation or loss of Drp1 function leads to slow down apoptosis and necrosis. Recent reports showed that patients who received consolidative radiotherapy (RT) combine R-CHOP had significant better 5-year event-free and overall survival rates than patients with diffuse large B-cell lymphoma who did not receive RT combination therapy. Although RT combination therapy significant increased survival of DLBCL, the mechanisms of RT induced cell death are reminded unclear. In this study, we investigated the roles of Drp1 activation in the sensitivity of DLBCL cells to radiotherapy. Radiation causes damage in both nuclear and mitochondrial DNAs and generation of reactive oxygen species (ROS) followed by caspase activation. In the radio-resistant DLBCL cells, radiation induced activation of Drp1, and led to mitochondrial fragmentation, caspase-3 activation and cell death. However, the sensitive DLBCL cells underwent cytochrome c release, caspase-3 activation and PARP cleavage but not the activation of Drip1. To confirm the role of Drp1 activation in radiation-induced cell death on radio-resistant cells, Drp1 was dephosphorylated by a serine kinase inhibitor STS. Co-treatment of radio-resistant DLBCL cells with STS and radiation greatly enhanced mitochondrial fragmentation and significantly increased the sensitivity of radio-resistant DLBCL cells to radiation-induced caspase-3 activation, PARP cleavage and apoptotic cell death. However, co-treatment with STS did not further increase the sensitivity of radio-sensitive cells to caspsase-3 activation and cell death. Our data indicate that radiation-induced cell death in radio-resistant DLBCL cells is regulated by Drp1. We therefore propose that Drp1 could be a potential target for overcoming radio-resistance. Disclosures: No relevant conflicts of interest to declare.

scholarly journals OREOCALLIS GRANDIFLORA PHOTOPROTECTIVE EFFECT AGAINST ULTRAVIOLET B RADIATION-INDUCED CELL DEATH

2018 ◽  
Vol 11 (2) ◽  
pp. 276 ◽  
Author(s):  
Vinueza D ◽  
Cajamarca D ◽  
Acosta K ◽  
Pilco G
Keyword(s):  
Cell Death ◽  
Ultraviolet B ◽  
Protection Factor ◽  
K Value ◽  
Hydroalcoholic Extract ◽  
E Coli ◽  
Rational Development ◽  
Radiation Induced ◽  
Positive Controls

Objective: The aim of this research was to evaluate the photoprotective effect of Oreocallis grandiflora hydroalcoholic extract (OGHE) againstultraviolet (UV)B-induced cell death model on a strain of Escherichia coli (ATCC 25922) and to determine the sun protection factor (SPF) using theequation proposed by Mansur.Methods: OGHE was obtained from leaves of O. grandiflora, following a standardized methodology. In short, O. grandiflora leaves were extracted withethanol 70% v/v and defatted with n-hexane, hydroalcoholic fraction was concentrated under controlled conditions through rotary evaporator, andfinally, the residue was freeze drying to obtain OGHE. The photoprotective effect was carried out using in vitro UVB-induced cell death model on astrain of E. coli (ATCC 25922), like a first approach to study its potential application on cosmetics.Results and Conclusions: From results, O. grandiflora is an important resource to produce new cosmetic products. However, the safety of OGHE isnecessary to a rational development in that sense. OGHE shows advantages in relation to conventional active compounds of commercial sunscreens usedin this research (2-ethylhexyl 4-methoxycinnamate and 2-ethylhexyl 4-(dimethylamino)benzoate) at the concentration of 2 mg/mL, on survivor time(with OGHE until 120 min), range of inactivation of E. coli caused by UVB (OGHE K value minor against to positive controls), and high SPF (13.56±0.21). 

The P-MAPA immunomodulator partially prevents apoptosis induced by Zika virus infection in THP-1 cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Morganna C. Lima ◽  
Elisa A. N. Azevedo ◽  
Clarice N. L. de Morais ◽  
Larissa I. O. de Sousa ◽  
Bruno M. Carvalho ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Virus Infection ◽  
Virus Replication ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Caspase 3 ◽  
Neurological Complications ◽  
Zika Virus Infection

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.

Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

2020 ◽  
Vol 17 (5) ◽  
pp. 716-724
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Antibacterial Agents ◽  
Sos Response ◽  
Luciferase Assay ◽  
Translational Machinery ◽  
E Coli ◽  
New Class

Background: The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique. Methods: We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay. Results: In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment. Conclusion: The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

Gamma Radiation Induced Effects on Cefuroxime and Cefotaxime. Investigation on Degradation and Syn-Anti Isomerization

1994 ◽  
Vol 20 (16) ◽  
pp. 2493-2508 ◽  
Author(s):  
E. Ciranni Signoretti ◽  
L. Valvo ◽  
P. Fattibene ◽  
S. Onori ◽  
M. Pantaloni
Keyword(s):  
Gamma Radiation ◽  
Radiation Induced
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