Silver nanoparticle enhances secretion of exosomes in SH-SY5Y cells: Potential therapeutic strategy for human neuroblastoma cancer

2021 ◽  
Vol 17 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim

Background: Exosomes—a subset of extracellular vesicles (EVs)—are secreted by virtually all cells, including human neuroblastoma cancer (SH-SY5Y) cells, into bodily fluids. Oxidative stress is critically involved in exosome biogenesis and release. Silver nanoparticles (AgNPs) induce cytotoxicity, oxidative stress, and apoptosis in cancer and non-cancer cells. Methods: Here, we studied whether AgNPs-induced oxidative stress could enhance exosome biogenesis and release under low serum conditions in the presence of AgNPs. Although several studies have reported various mechanisms that contribute to EV biogenesis and release from cells, none exists on the involvement of external stimuli by controlling acetylcholinesterase (AChE) and neutral-sphingomyelinase (n-SMase) activities, total protein concentration of exosomes, and exosome count. Results: Owing to cytotoxic and oxidative stresses, AgNPs-treated cells and exosome release were significantly facilitated, which strongly correlated with the AgNPs-induced oxidative stress. Moreover, the expression levels of some important exosome biomarkers were found to be significant under oxidative stress conditions. N-acetylcysteine prevented oxidative stress-induced exosome biogenesis and release. Furthermore, we identified the involvement of the ceramide pathway in exosome functions by inhibiting AChE and n-SMase activities, and exosome protein/counts. These data contribute to the understanding of how AgNPs and intracellular molecular pathways affect exosome biogenesis and release in SH-SY5Y cells. Conclusion: To the best of our knowledge, this is the first study showing that AgNPs stimulate exosome biogenesis and release by inducing oxidative stress and ceramide pathways.

2020 ◽  
Vol 64 (1) ◽  
pp. 187-195
Author(s):  
Bogdan Sidonia ◽  
Rafa Horatiu ◽  
Luca Vlad ◽  
Dulf Francisc ◽  
Ober Ciprian ◽  
...  

AbstractIntroductionOxidative stress (OS) seems to be an important mediator of cellular injury, from which sepsis can proceed. Studies have demonstrated the protective effect of controlled hypothermia in sepsis. This study aimed to evaluate its effects on OS parameters in rat hepatic and renal tissue septic after caecal ligation and puncture (CLP).Material and MethodsThree groups were appointed (10 rats/group): C (control), SN (sepsis normothermic), and SH (sepsis hypothermic). Ten hours from CLP, the liver and kidneys were harvested and total protein concentration, superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, lipid peroxidation level (malondialdehyde (MDA), carbonylated proteins (2,4-dinitrophenylhydrazine (DNPH), and fatty acid profile were analysed.ResultsSepsis significantly increased SOD and GPx activities in the liver, regardless of the temperature. In renal tissue, GPx activity increased significantly in normothermic conditions and SOD tended to decrease in hypothermic conditions. MDA and DNPH concentrations increase in both tissues after CLP. Hypothermia significantly lowered MDA in the liver but only changed it insignificantly in the kidneys. The DNPH in the liver and kidneys was significantly lower in hypothermic conditions. The unsaturated-to-saturated fatty acids ratio was significantly lower in sepsis, and the fall in temperature raised this ratio.ConclusionExperimentally induced sepsis in rats enhances OS in the liver and kidneys. The effect of hypothermia on OS indices is dependent on the type of tissue.


2020 ◽  
Vol 16 ◽  
Author(s):  
Mini Dahiya ◽  
Monu Yadav ◽  
Kalpana Nagpal ◽  
Nidhi Sharma ◽  
Kajal Joshi ◽  
...  

: Prostate Cancer (PC) is one the most prominent cause of deaths in males worldwide especially in western countries. The exhaustive research into prostate cancer to date has demonstrated ELAC2, RNASEL, MSR1, NBS1, CHEK2, MYC, BCL-2, c-Kit, tumor suppressor genes, BRCA1, BRCA2, PACE4, GSTP1, PTEN,CDKN1B, NKX3.1, KLF6, FOXA1, Retinoblastoma, p53, androgen receptor, kallikreins, ETS, CYP17, SRD5A2, E-cadherin, KAI1/CD82, hepsin, AMACR, PIM1, MTA-1, EZH2, EPHB2, growth factors & its receptors, cannabinoid receptors, annexins, oxidative stress and inflammation are entailed changes underlying the initiation, development, and progression of PC. Furthermore, oncology would shift from a reactive to proactive discipline so exploring these targets open new area of research. Therefore, the present review is focused on molecular pathophysiology biomarkers for the progression of PC that would encourage the researchers and pharmaceutical industries to investigate potential therapeutic strategy to overcome demerits of currently available clinically therapies.


2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.


2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.


2020 ◽  
Vol 14 ◽  
pp. 117863022093839
Author(s):  
Tania Rahman ◽  
Ar-Rafi Md. Faisal ◽  
Tahura Khanam ◽  
Hossain Uddin Shekhar

Perennial indoor environmental pollution in the textile industrial area is a potential health hazard for workers engaged in this line of work, resulting in mental aberration to severe health risks. This study was designed to investigate the indoor environmental quality of textile industries and correlate its effect on the occupational health and well-being of the textile workers by measuring plasma oxidative stress status in textile workers and healthy control subjects. Environmental samples were collected from 15 textile industries located in Dhaka division, and 30 volunteer textile workers and 30 volunteer office workers (control) aged 18 to 57 years participated in the study. The concentration of plasma ascorbic acid (P-ASC), plasma malondialdehyde (P-MDA), and plasma conjugated diene (P-CD) was measured in both groups. The noise level (78.0 ± 0.68 dB) and the formaldehyde level (141.80 ± 4.47 µg/m3) were found to be significantly higher in the indoor environmental area compared with those in the control area (70.17 ± 0.25 dB and 108.0 ± 0.76 µg/m3, respectively). Furthermore, the daily average concentration of suspended particulate matters (PMs), that is, PM2.5 (322.2 ± 13.46 µg/m3) and PM10 (411.0 ± 17.57 µg/m3), was also found to be significantly higher in the indoor environmental air compared with that in the control area (78.59 ± 1.66 and 174.0 ± 2.33 µg/m3, respectively). The levels of P-MDA (0.37 ± 0.03 nmol/L) and P-CD (14.74 ± 0.61 nmol/L) were significantly increased, whereas the level of P-ASC level (0.46 ± 0.04 mg/dL) was markedly decreased in the textile workers compared with the healthy control subjects (0.18 ± 0.01 nmol/L of P-MDA, 10.04 ± 0.44 nmol/L of P-CD, and 1.29 ± 0.06 mg/dL of P-ASC). The textile plants were found to have significantly elevated levels of indoor environmental pollutants compared with those in the control area, and the textile workers were significantly exposed to oxidative stresses compared with the control subjects. The use of noise pads and high-efficiency air filters is perhaps highly instrumental to put an end to this prevailing situation. Moreover, to overcome the oxidative stresses among workers, supplementation of antioxidant vitamins (ie, ascorbic acid and/or vitamin E) may be beneficial. In addition, to prevent serious health-related issues, proper precautions should be taken to protect the occupational health of the textile workers.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 539
Author(s):  
Santa Cirmi ◽  
Alessandro Maugeri ◽  
Giovanni Enrico Lombardo ◽  
Caterina Russo ◽  
Laura Musumeci ◽  
...  

Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.


2014 ◽  
Vol 27 (1) ◽  
pp. 253-257 ◽  
Author(s):  
Patrick Marcel Seumo Tchekwagep ◽  
Charles Péguy Nanseu-Njiki ◽  
Emmanuel Ngameni ◽  
Ravi Danielsson ◽  
Thomas Arnebrant ◽  
...  

2016 ◽  
Vol 43 (7) ◽  
pp. 607 ◽  
Author(s):  
Souid Aymen ◽  
Gabriele Morena ◽  
Longo Vincenzo ◽  
Pucci Laura ◽  
Bellani Lorenza ◽  
...  

In this work we studied the effect of salinity (ranging from 50 to 500 mM NaCl) on the physiological and the antioxidant responses of the local halophyte Limonium delicatulum Kuntze. We based our analysis on 12 biochemical assays that are commonly used to measure the antioxidant responses under stress such as oxidative stress markers, enzymes activities and polyphenolic compounds. Our aim was to study parameters that are strongly correlated with the growth response to salinity. Results showed two different growth responses depending on the concentration of NaCl in the medium. Under 50 to 200 mM, the growth was stimulated before it decreased significantly at 300–500 mM. L. delicatulum revealed a good aptitude to maintain photosynthetic machinery by increasing the concentrations of photosynthetic pigments, which is essential for the stabilisation of photosystems and the photosynthesis process under optimal NaCl concentration. Their breakdown at higher salinity decreased the photosynthetic performance of plants resulting in growth inhibition. Moreover, to reduce the damaging effect of oxidative stress and to tolerate the accumulation of salt ions, L. delicatulum induced the activities of their antioxidant enzymes more than their contents in polyphenolic compounds.


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