scholarly journals S-ethyl ethanethiosulfinate, a derivative of allicin, induces metacaspase-dependent apoptosis through ROS generation in Penicillium chrysogenum

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Feilong Qi ◽  
Chen Zhang ◽  
Shanshan Jiang ◽  
Qian Wang ◽  
Kudelaidi Kuerban ◽  
...  

AbstractAllicin can be used as fumigant to protect food and cultural relics from fungal contamination because of its strong antifungal activity and the characteristics of high volatility and no residues. However, the obvious disadvantages such as high minimal inhibitory concentration and instability prevent it from wide application. In this study, a stable derivative of allicin, S-ethyl ethanethiosulfinate (ALE), was synthesized. We further explored its antifungal activity and apoptosis-inducing effect, as well as the underlying mechanism. ALE had an excellent capability of inhibiting spore germination and mycelial growth of Penicillium chrysogenum observed by inverted microscope and scanning electron microscopy. XTT colorimetric assay indicated ALE could reduce the cell viability obviously and IC50 was 0.92 μg/ml, only 1/42 of allicin (38.68 μg/ml). DHR 123 ROS Assay Kit, flow cytometry assay and confocal immunofluorescence revealed intercellular ROS generation and metacaspase-dependent apoptosis triggered by ALE, while antioxidant tocopherol could reverse ALE-induced cytotoxicity effect and metacaspase activation. These results indicate that ALE induces metacaspase-dependent apoptosis through ROS generation, thus possesses an effective antifungal activity. This new derivative of allicin might be developed as a high efficient alternative to the conventional fungicides for food storage and cultural relic protection.

2021 ◽  
Vol 1 (3) ◽  
pp. 26-32
Author(s):  
M.N. Lokachuk ◽  
◽  
O.A. Savkina ◽  
E.A. Pavlovskaja ◽  
Yu.M. Frolova ◽  
...  

В статье рассмотрена возможность применения заквасок для подавления плесневения хлеба. Целью работы являлось изучение влияния заквасок, приготовленных на чистых культурах заквасочных микроорганизмов, на скорость плесневения ржано-пшеничного и пшеничного хлебов. Исследования проводились в Санкт-Петербургском филиале ФГАНУ НИИХП в рамках темы госзадания № 2593-2014-0018 «Разработать научные основы формирования микробных композиций и биосистем на их основе, обеспечивающих высокое качество и безопасность хлебобулочных изделий». Объектами исследования являлись ржано-пшеничные и пшеничные хлеба, выработанные как с использованием заквасок, так и ускоренным способом. Для выявления влияния технологии приготовления хлеба на скорость развития плесени, проводили модельные опыты с заражением его стерильных ломтиков чистой культурой плесневых грибов Penicillium chrysogenum. В статье приведен обзор антимикробных метаболитов молочнокислых бактерий, обусловливающих их фунгицидную активность, рассмотрен механизм их воздействия на плесневые грибы. Установлено, что применение ржаной густой закваски в количестве 25 % муки в закваске имело наибольший фунгицидный эффект при хранении хлеба. Применение КМКЗ в количестве 20 % муки в закваске позволило замедлить плесневение на 1–1,5 суток по сравнению с контролем без закваски на подкисляющей добавке «Цитрасол». В результате проведенных исследований показано, что на скорость развития плесневых грибов оказывает влияние содержание уксусной кислоты в готовых изделиях, которая накапливается в процессе брожения разных видов заквасок.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Viktoria Dobrocsyova ◽  
Miroslava Slamkova ◽  
Katarina Krskova ◽  
Lucia Balazova ◽  
Maciej Suski ◽  
...  

Angiotensin 1-7 (Ang 1-7) enhances insulin signaling and glucose transport activity in the skeletal muscle. The aim of our study was to evaluate the effect of AVE0991, a nonpeptide Mas receptor agonist, on the metabolic parameters, expression of RAS components and markers of oxidative stress, and insulin signaling in the skeletal morbidly obese rats. 33-week-old male obese Zucker rats were treated with vehicle and AVE0991 (0.5 mg/kg BW/day) via osmotic minipumps for two weeks. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps. The enzymatic activities were detected flourometrically (aminopeptidase A) or by colorimetric assay kit (protein tyrosine phosphatase 1B). Administration of AVE0991 enhanced insulin signaling cascade in the skeletal muscle, reflected by improved whole-body glucose tolerance. It has been shown that reactive oxygen species (ROS) have insulin-mimetic action in muscle. The expression of renin receptor, transcription factor PLZF, and prooxidant genes was upregulated by AVE0991 accompanied by elevated expression of genes coding enzymes with antioxidant action. Our results show that AVE0991 administration activates genes involved in both ROS generation and clearance establishing a new prooxidant/antioxidant balance on a higher level, which might contribute to the improved insulin signaling pathway and glucose tolerance of obese Zucker rats.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elisa Martino ◽  
Daniela Cristina Vuoso ◽  
Stefania D’Angelo ◽  
Luigi Mele ◽  
Nunzia D’Onofrio ◽  
...  

Abstract Polyphenols represent the most studied class of nutraceuticals that can be therapeutics for a large spectrum of diseases, including cancer. In this study, we investigated for the first time the antitumor activities of polyphenol extract from Annurca apple (APE) in MDA-MB-231 triple negative breast cancer cells, and we explored the underlying mechanisms. APE selectively inhibited MDA-MB-231 cell viability and caused G2/M phase arrest associated with p27 and phospho-cdc25C upregulation and with p21 downregulation. APE promoted reactive oxygen species (ROS) generation in MDA-MB-231 cells while it acted as antioxidant in non-tumorigenic MCF10A cells. We demonstrated that ROS generation represented the primary step of APE antitumor activity as pretreatment with antioxidant N-acetylcysteine (NAC) prevented APE-induced G2/M phase arrest, apoptosis, and autophagy. APE downregulated Dusp-1 and induced a significant increase in JNK/c-Jun phosphorylation that were both prevented by NAC. Moreover, downregulation of JNK by its specific inhibitor SP600125 significantly diminished the anticancer activity of APE indicating that ROS generation and sustained JNK activation represented the main underlying mechanism of APE-induced cell death. APE also inhibited AKT activation and downregulated several oncoproteins, such as NF-kB, c-myc, and β-catenin. In light of these results, APE may be an attractive candidate for drug development against triple negative breast cancer.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12028-e12028
Author(s):  
Guangji Wang ◽  
Jiye Aa ◽  
Chun Ge

e12028 Background: Continuous exposure of breast cancer cells to adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and reduced glutathione (GSH) biosynthesis, while N-acetylcysteine, the ROS scavenger, reversed the over-expressed P-gp induced by ADR. Methods: Based on MCF-7 breast cancer cells and the adriamycin-resistant MCF-7 subline (MCF-7R), we investigated the P-gp expression on mRNA, protein and function level by qPCR, western blotting, flow cytometry and laser scanning confocal and so on, under SLC7A11 down-regulation/over-expression, cystine depletion/supplement, increased ROS generation and combined factors. Results: The present study showed that ADR inhibited cystine influx (source material of GSH) and SLC7A11 transporter (in charge of cystine uptake) in MCF-7 cells. For the first time, we showed that a down-regulation/silence of SLC7A11, or cystine deprivation, or an enhanced exposure of ROS agents directly and significantly increased P-gp expression; yet, a combination of either an inhibited/silenced SLC7A11 or cystine deprivation and an increased ROS dramatically promoted the P-gp expression in MCF-7 cells. On the contrary, an over-expression of SLC7A11, or sufficiently supplementary cystine, or scavenger of ROS significantly depressed P-gp expression and activity. Moreover, the down-regulation of SLC7A11 and cystine deprivation induced an elevation of ROS and P-gp that could be reversed by N-acetylcysteine. It was suggested that ROS and SLC7A11/cystine were the two relevant factors responsible for the upregulated expression and function of P-gp. Conclusions: This study provided the direct evidences suggesting that ROS triggered over-expression of P-gp and demonstrated that the combination of either an inhibition of SLC7A11 or cystine influx and elevated ROS was the underlying mechanism contributing to P-gp over-expression induced by ADR. It was indicated that the SLC7A11 might be a potential target modulating ADR resistance.


2014 ◽  
Vol 33 (5) ◽  
pp. 412-418 ◽  
Author(s):  
Eun Joo Pak ◽  
Gi Dong Son ◽  
Byung Sun Yoo

Cadmium, a highly ubiquitous heavy metal, is well known to induce neurotoxicity. However, the underlying mechanism of cadmium-mediated neurotoxicity remains unclear. We have studied cadmium inhibition of neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all- trans-retinoic acid (RA). Cadmium, at a concentration of 3 μmol/L, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells 48 hours after cadmium treatment (1-3 μmol/L cadmium) was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 1 to 3 μmol/L cadmium resulted in decreased level of cross-reactivities with 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The reactive oxygen species (ROS) scavenger, NAC (N-acetyl-l-cysteine), recovered the expression of GAP-43 in cadmium-treated cells. The results indicate that cadmium is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells and that this effect might result from ROS generation by cadmium.


2017 ◽  
Vol 5 (9) ◽  
pp. 7912-7919 ◽  
Author(s):  
Yuan Zhao ◽  
Yaodong Luo ◽  
Yingyue Zhu ◽  
Yali Sun ◽  
Linyan Cui ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ershun Liang ◽  
Xue Liu ◽  
Zhanhui Du ◽  
Ruixue Yang ◽  
Yuxia Zhao

Andrographolide (Andro), a major bioactive component obtained from Andrographis paniculata Nees, has exerted wide antioxidant as well as cytoprotective properties. However, whether Andro treatment could retard the progress of diabetic cardiomyopathy (DCM) remains unknown. In this study, we evaluated the effects of Andro against diabetes-induced myocardial dysfunction and explored the underlying mechanism in STZ-induced diabetic mice. As a result, treatment with Andro dose dependently suppressed cardiac inflammation and oxidative stress, accompanied by decreasing cardiac apoptosis, which subsequently ameliorated cardiac fibrosis and cardiac hypertrophy. Further, Andro blocked hyperglycemia-triggered reactive oxygen species (ROS) generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Our results suggest that the cardioprotective effects afforded by Andro treatment involve the modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. The present study unravels the therapeutic potential of Andro in the treatment of DCM by attenuating oxidative stress, inflammation, and apoptosis.


2017 ◽  
Vol 43 (1) ◽  
pp. 209-222 ◽  
Author(s):  
Xuexian Tan ◽  
Xiaohe Zheng ◽  
Zena Huang ◽  
Jiaqiong Lin ◽  
Chuli Xie ◽  
...  

Background: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. Methods: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells. Results: Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression. Conclusion: S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target.


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