The Mitochondrial-Targeted Peptide, SS31, Protects Murine 661W Cells from Oxidative Damage via Induction of Autophagy

2020 ◽  
Vol 16 (5) ◽  
pp. 603-615
Author(s):  
Yuan He ◽  
Beilei He ◽  
Ruixue Zhang ◽  
Zhuoya Quan ◽  
Yun Xu ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Annexin V ◽  
Illumina Platform ◽  
Associated Proteins ◽  
Significant Attenuation ◽  
Pre Treatment ◽  
The Impact ◽  
Do So

The goal of this study was to examine the impact of the mitochondrial-targeted antioxidant peptide, SS31, and its role in promoting autophagy in cone photoreceptor 661W cells that were subjected to oxidative damage. To do so, we examined the viability of 661W cells in the presence of increasing concentrations of H2O2 with or without SS31 pre-treatment using the MTT assay and by expression of autophagy and apoptosis-associated proteins LC3-II/I, P62, and caspase-3. Autophagy was evaluated by fluorescence microscopy in cells stained with monodansyl cadaverine (MDC). Autophagy was induced with rapamycin (Rap) and inhibited with bafamycin A1 (bafA1) followed by examination of Reactive oxygen species (ROS) levels in target 661W cells by fluorescence microscopy and flow cytometry. Annexin V/PI staining was used to evaluate the rate of apoptosis and mRNA sequencing (mRNA-seq) analysis (Illumina platform) was performed on H2O2-exposed 661W cells treated with SS31. Among our results, we observed a substantial and concentration-dependent decrease in 661W cell viability in response to H2O2-exposure; production of ROS, autophagy and apoptosis were induced at 8 h in response to exposure to 100 μM of H2O2. Pre-treatment with 100 nM SS31 resulted in significant attenuation of H2O2-mediated cytotoxicity, together with reduced ROS production and enhanced autophagy observed in response to oxidative stress. Both Rap and bafA1 were used to modulate SS31-mediated autophagy; the impact of Rap was similar to that of SS31. By contrast, administration of bafA1 counteracted autophagy induced by SS31. Furthermore, mRNAseq analysis revealed that SS31 promoted significant alterations in gene expression in 661W cells and suggested that autophagy was induced via the mTORC1-mediated signaling. In conclusion, our results indicate that exposure to H2O2 resulted in reduced 661W cell viability via mechanisms associated with oxidative damage, apoptosis, and autophagy. Notably, we demonstrated that pre-treatment with SS31 protects 661W cells from H2O2-induced oxidative damage that may result in part from induction of autophagy via mTORC1-mediated signaling pathways.

scholarly journals Effects of drinking desalinated seawater on cell viability and proliferation

2017 ◽  
Vol 15 (3) ◽  
pp. 360-366
Author(s):  
Camila Longhi Macarrão ◽  
André Luis Lacerda Bachi ◽  
Mario Mariano ◽  
Lucia Jamli Abel
Keyword(s):  
Cell Viability ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Dependent Manner ◽  
Health Food ◽  
Murine Embryonic Fibroblast ◽  
Beneficial Effects ◽  
Mineral Components ◽  
Pre Treatment ◽  
Diphenyl Tetrazolium Bromide

Desalination of seawater is becoming an important means to address the increasing scarcity of freshwater resources in the world. Seawater has been used as drinking water in the health, food, and medical fields and various beneficial effects have been suggested, although not confirmed. Given the presence of 63 minerals and trace elements in drinking desalinated seawater (63 DSW), we evaluated their effects on the behavior of tumorigenic and nontumorigenic cells through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and annexin-V-fluorescein isothiocyanate/propidium iodide staining. Our results showed that cell viability and proliferation in the presence of 63 DSW were significantly greater than in mineral water and in the presence of fetal bovine serum in a dose-dependent manner. Furthermore, 63 DSW showed no toxic effect on murine embryonic fibroblast (NIH-3T3) and murine melanoma (B16-F10) cells. In another assay, we also showed that pre-treatment of non-adherent THP-1 cells with 63 DSW reduces apoptosis incidence, suggesting a protective effect against cell death. We conclude that cell viability and proliferation were improved by the mineral components of 63 DSW and this effect can guide further studies on health effects associated with DSW consumption.

scholarly journals Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 473 ◽  
Author(s):  
Maria Elisabetta Clementi ◽  
Beatrice Sampaolese ◽  
Francesca Sciandra ◽  
Giuseppe Tringali
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Target Genes ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Radiation Induced ◽  
Pre Treatment

The oxidative damage of the retinal pigment epithelium (RPE) is the early event that underlies the pathogenesis of maculopathies. Numerous studies have shown that punicalagin (PUN), a polyphenol present in pomegranate, can protect several cell types from oxidative stress. Our study aims to establish if PUN protects RPE from UV radiation-induced oxidative damage. We used an experimental model which involves the use of a human-RPE cell line (ARPE-19) exposed to UV-A radiation for 1, 3, and 5 h. ARPE-19 cells were pre-treated with PUN (24 h) followed by UV-A irradiation; controls were treated identically, except for UV-A. Effects of pre-treatment with PUN on cell viability, intracellular reactive oxygen species ROS levels, modulation of Nrf2 and its antioxidant target genes, and finally apoptosis were examined. We found that pre-treatment with PUN: (1) antagonized the decrease in cell viability and reduced high levels of ROS associated with UV-A-induced oxidative stress; (2) activated Nrf2 signaling pathway by promoting Nrf2 nuclear translocation and upregulating its downstream antioxidant target genes (HO-1 and NQO1); (3) induced an anti-apoptotic effect by decreasing Bax/Bcl-2 ratio. These findings provide the first evidence that PUN can prevent UV-A-induced oxidative damage in RPE, offering itself as a possible antioxidant agent capable of contrasting degenerative eye diseases.

Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  
Keyword(s):  
Vitamin E ◽  
Cell Viability ◽  
Neuronal Cells ◽  
Positive Control ◽  
Post Treatment ◽  
Mitochondrial Activity ◽  
Before And After ◽  
Pre Treatment ◽  
Tocotrienol Rich Fraction ◽  
Major Mediator

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

2018 ◽  
Vol 18 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Aikebaier Maimaiti ◽  
Amier Aili ◽  
Hureshitanmu Kuerban ◽  
Xuejun Li
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Gallic Acid ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

Reconstituting the International, 1918–1923

2017 ◽  
Author(s):  
Talbot C. Imlay
Keyword(s):  
Seismic Events ◽  
Great War ◽  
Bolshevik Revolution ◽  
Meaning And Purpose ◽  
Post War ◽  
The Impact ◽  
First Time ◽  
The Great War ◽  
Do So ◽  
Lengthy Process

This chapter examines the post-war efforts of European socialists to reconstitute the Socialist International. Initial efforts to cooperate culminated in an international socialist conference in Berne in February 1919 at which socialists from the two wartime camps met for the first time. In the end, however, it would take four years to reconstitute the International with the creation of the Labour and Socialist International (LSI) in 1923. That it took so long to do so is a testimony to the impact of the Great War and to the Bolshevik revolution. Together, these two seismic events compelled socialists to reconsider the meaning and purpose of socialism. The search for answers sparked prolonged debates between and within the major parties, profoundly reconfiguring the pre-war world of European socialism. One prominent stake in this lengthy process, moreover, was the nature of socialist internationalism—both its content and its functioning.

scholarly journals Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism

2021 ◽  
Author(s):  
Michael V. Lombardo ◽  
Elena Maria Busuoli ◽  
Laura Schreibman ◽  
Aubyn C. Stahmer ◽  
Tiziano Pramparo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Outcome ◽  
Early Intervention ◽  
Developmental Change ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Time In Treatment ◽  
Pre Treatment ◽  
Blood Leukocyte ◽  
The Impact

AbstractEarly detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.

scholarly journals Time-to-Treatment in Oral Cancer: Causes and Implications for Survival

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1321
Author(s):  
Constanza Saka-Herrán ◽  
Enric Jané-Salas ◽  
Antoni Mari-Roig ◽  
Albert Estrugo-Devesa ◽  
José López-López
Keyword(s):  
Oral Cancer ◽  
Previous Treatment ◽  
Diagnostic Procedures ◽  
Original Data ◽  
Primary Treatment ◽  
Medical Attention ◽  
Time Interval ◽  
Pre Treatment ◽  
The Impact ◽  
Lack Of Knowledge

The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.

scholarly journals Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3256
Author(s):  
Adam Brewczyński ◽  
Beata Jabłońska ◽  
Agnieszka Maria Mazurek ◽  
Jolanta Mrochem-Kwarciak ◽  
Sławomir Mrowiec ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Oropharyngeal Cancer ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Post Treatment ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Hpv Status ◽  
Pre Treatment ◽  
The Impact

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

scholarly journals Anthracycline-induced cytotoxicity in the GL261 glioma model system

2021 ◽  
Author(s):  
Amber M. Tavener ◽  
Megan C. Phelps ◽  
Richard L. Daniels
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Effects ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Gl261 Glioma

AbstractGlioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.

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