Exposure to the Neurotoxic Dinoflagellate,Alexandrium catenella,Induces Apoptosis of the Hemocytes of the Oyster,Crassostrea gigas

This study assessed the apoptotic process occurring in the hemocytes of the Pacific oyster, Crassostrea gigas, exposed to Alexandrium catenella, a paralytic shellfish toxins (PSTs) producer. Oysters were experimentally exposed during 48 h to the toxic algae. PSTs accumulation, the expression of 12 key apoptotic-related genes, as well as the variation of the number of hemocytes in apoptosis was measured at time intervals during the experiment. Results show a significant increase of the number of hemocytes in apoptosis after 29 h of exposure. Two pro-apoptotic genes (Bax and Bax-like) implicated in the mitochondrial pathway were significantly upregulated at 21 h followed by the overexpression of two caspase executor genes (caspase-3 and caspase-7) at 29 h, suggesting that the intrinsic pathway was activated. No modulation of the expression of genes implicated in the cell signaling Fas-Associated protein with Death Domain (FADD) and initiation-phase (caspase-2) was observed, suggesting that only the extrinsic pathway was not activated. Moreover, the clear time-dependent upregulation of five (Bcl2, BI-1, IAP1, IAP7B and Hsp70) inhibitors of apoptosis-related genes associated with the return to the initial number of hemocytes in apoptosis at 48 h of exposure suggests the involvement of strong regulatory mechanisms of apoptosis occurring in the hemocytes of the Pacific oyster.     

Effects of in vitro brevetoxin exposure on apoptosis and cellular metabolism in a leukemic T cell line (Jurkat)

Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat) as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan), respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 – 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3.     

Stimulation of Neurite Outgrowth in Cerebrocortical Neurons by Sodium Channel Activator Brevetoxin-2 Requires Both N-Methyl-D-aspartate Receptor 2B (GluN2B) and p21 Protein (Cdc42/Rac)-Activated Kinase 1 (PAK1)

N-methyl-D-aspartate (NMDA) receptors play a critical role in activity-dependent dendritic arborization, spinogenesis, and synapse formation by stimulating calcium-dependent signaling pathways. Previously, we have shown that brevetoxin 2 (PbTx-2), a voltage-gated sodium channel (VGSC) activator, produces a concentration-dependent increase in intracellular sodium [Na⁺]_I and increases NMDA receptor (NMDAR) open probabilities and NMDA-induced calcium (Ca²⁺) influxes. The objective of this study is to elucidate the downstream signaling mechanisms by which the sodium channel activator PbTx-2 influences neuronal morphology in murine cerebrocortical neurons. PbTx-2 and NMDA triggered distinct Ca²⁺-influx pathways, both of which involved the NMDA receptor 2B (GluN2B). PbTx-2-induced neurite outgrowth in day in vitro 1 (DIV-1) neurons required the small Rho GTPase Rac1 and was inhibited by both a PAK1 inhibitor and a PAK1 siRNA. PbTx-2 exposure increased the phosphorylation of PAK1 at Thr-212. At DIV-5, PbTx-2 induced increases in dendritic protrusion density, p-cofilin levels, and F-actin throughout the dendritic arbor and soma. Moreover, PbTx-2 increased miniature excitatory post-synaptic currents (mEPSCs). These data suggest that the stimulation of neurite outgrowth, spinogenesis, and synapse formation produced by PbTx-2 are mediated by GluN2B and PAK1 signaling.     

42℃极端高温胁迫对木薯单爪螨(Mononychellus mcgregori)保护酶及热激蛋白基因表达的影响

木薯单爪螨(Mononychellus mcgregori)是新入侵中国的木薯重要害螨,原产地为南美洲,是一种热带土著害螨,近年来该螨扩张范围不断增大,对高温的适应性是其种群扩散的重要前提。本研究发现,42℃极端高温胁迫1 h后,木薯单爪螨成螨保护酶基因PPO、POD、As A-POD、CAT和Cu/Zn SOD的相对表达量显著升高,分别高达对照的5.19、4.38、152.23、321.42和3.41倍,且与其酶活性变化趋势存在一致性,酶活性值分别升高为对照的1.81、12.52、9.00、1.75和1.14倍。热激蛋白基因Hsp70的相对表达量显著升高,为对照的56.85倍。因此说明,保护酶POD、As A-POD、CAT、SOD和PPO以及热激蛋白Hsp70可能在木薯单爪螨应对高温胁迫中具有重要作用,高温下保护酶及热激蛋白Hsp70基因表达量及其活性的升高可能导致木薯单爪螨对高温的耐受能力逐渐增强,从而逐渐适应热区高温环境,并可能增强其后续的繁殖能力而使其种群不断增长,扩张范围不断增强。     

A Feedback Mechanism to Control Apoptosis Occurs in the Digestive Gland of the Oyster Crassostrea gigas Exposed to the Paralytic Shellfish Toxins Producer Alexandrium catenella

To better understand the effect of Paralytic Shellfish Toxins (PSTs) accumulation in the digestive gland of the Pacific oyster, Crassostrea gigas, we experimentally exposed individual oysters for 48 h to a PSTs producer, the dinoflagellate Alexandrium catenella. In comparison to the effect of the non-toxic Alexandrium tamarense, on the eight apoptotic related genes tested, Bax and BI.1 were significantly upregulated in oysters exposed 48 h to A. catenella. Among the five detoxification related genes tested, the expression of cytochrome P450 (CYP1A) was shown to be correlated with toxin concentration in the digestive gland of oysters exposed to the toxic dinoflagellate. Beside this, we observed a significant increase in ROS production, a decrease in caspase-3/7 activity and normal percentage of apoptotic cells in this tissue. Taken together, these results suggest a feedback mechanism, which may occur in the digestive gland where BI.1 could play a key role in preventing the induction of apoptosis by PSTs. Moreover, the expression of CYP1A, Bax and BI.1 were found to be significantly correlated to the occurrence of natural toxic events, suggesting that the expression of these genes together could be used as biomarker to assess the biological responses of oysters to stress caused by PSTs.     

Effects of copper and superoxide dismutase content of seminal plasma on buffalo semen characteristics

To investigate the effects of copper and superoxide dismutase (SOD) content of seminal plasma on buffalo semen characteristics, 54 semen samples collected from buffalo bulls by a bovine artificial vagina were used. Semen characteristics (motility, viability, morphology, concentration and volume) were recorded. Seminal plasma was harvested by centrifugation and kept frozen until analysis. Seminal plasma copper content was determined by atomic absorption procedure and SOD was measured by using a kit. The mean total copper value of seminal plasma was recorded as 2.51 +/- 0.04 mg kg(-1) (Mean +/- SEM) and the mean total SOD values was 39.02 +/- 0.81 IU mL(-1). To reduce the range of variability, the data were categorized according to their motility records in 3 groups of Excellent (Ex, >90% motile, n = 33), Good (Go, 80-89% motile, n = 15) and Moderate (Mo, < 79% motile, n = 6). The mean motility, viability, copper and SOD values in Ex group was recorded as 92.24 +/- 0.51%, 94.00 +/- 0.48%, 2.56 +/- 0.04 mg kg(-1) and 39.52 +/- 0.57 IU mL(-1), respectively. These values were 81.66 +/- 0.62%, 85.26 +/- 0.95%, 2.38 +/- 0.11 mg kg(-1) and 36.48 +/- 1.51 IU mL(-1) in Go group and 71.66 +/- 1.05%, 77.00 +/- 2.94%, 2.55 +/- 0.10 mg kg(-1) and 50.66 +/- 2.51 in Mo group, respectively. The mean copper value in Ex group was highly (r = 0.600) correlated with SOD and correlated with sperm motility (r = 0.372) and viability (r = 0.363), while, in Go group it was highly correlated (r = 0.945) with SOD and sperm viability (r = 0.652) and in Mo group it was correlated (r = 0.874) with semen volume only. The mean SOD values in Ex group was highly correlated with sperm motility (r = 0.492) and viability (r = 0.490) and mean copper values, in Go group, it was highly correlated whit sperm viability (r = 0.659) and mean copper values and in Mo group it had no significant correlations with semen parameters. These results suggest that copper and SOD content of the buffalo seminal plasma have an influence on the sperm motility and viability which are the most important factors in semen fertility.     

Oyster-Derived Tyr-Ala (YA) Peptide Prevents Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure by Suppressing Inflammatory,Apoptotic, Ferroptotic,and Pyroptotic Signals

Models created by the intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-GalN) have been widely used to study the pathogenesis of human acute liver failure (ALF) and drug development. Our previous study reported that oyster (Crassostrea gigas) hydrolysate (OH) had a hepatoprotective effect in LPS/D-GalN-injected mice. This study was performed to identify the hepatoprotective effect of the tyrosine-alanine (YA) peptide, the main component of OH, in a LPS/D-GalN-injected ALF mice model. We analyzed the effect of YA on previously known mechanisms of hepatocellular injury in the model. LPS/D-GalN-injected mice showed inflammatory, apoptotic, ferroptotic, and pyroptotic liver injury. The pre-administration of YA (10 mg/kg or 50 mg/kg) significantly reduced the liver damage factors. The hepatoprotective effect of YA was higher in the 50 mg/kg YA pre-administered group than in the 10 mg/kg YA pre-administered group. These results showed that YA had a hepatoprotective effect by reducing inflammation, apoptosis, ferroptosis, and pyroptosis in the LPS/D-GalN-injected ALF mouse model. We suggest that YA can be used as a functional peptide for the prevention of acute liver injury.     

Temporal Dynamics of Antioxidant Defence System in Relation to Polyamine Catabolism in Rice under Direct-Seeded and Transplanted Conditions

Six rice cultivars viz. PR120, PR116, Feng Ai Zan, PR115, PAU201 and Punjab Mehak 1 under the direct-seeded and transplanted conditions were used to investigate the involvement of antioxidative defence system in relation to polyamine catabolism in temporal regulation of developing grains. Activities of ascorbate peroxidase(APx), guaiacol peroxidase(GPx), catalase(CAT), superoxide dismutase(SOD), polyamine oxidases(PAO) and contents of ascorbate, α-tocopherol, proline and polyamines increased gradually until mid-milky stage and then declined towards maturity stage under both planting conditions. The transplanted condition led to higher activities of antioxidative enzymes(APx, GPx and CAT) and contents of ascorbate, α-tocopherol and proline whereas the direct-seeded condition had elevated levels of PAO and SOD activities and contents of polyamines, lipid peroxide and hydrogen peroxide. Cultivars Feng Ai Zan and PR120 exhibited superior tolerance over other cultivars by accumulating higher contents of ascorbate, α-tocopherol and proline with increasing level of PAO and SOD activities under the direct-seeded condition. However, under the transplanted condition PR116 and PAU201 showed higher activities of antioxidative enzymes with decreasing content of lipid peroxide. Therefore, we concluded that under the direct-seeded condition, enhancements of polyamines content and PAO activity enabled rice cultivars more tolerant to oxidative stress, while under the transplanted condition, antioxidative defence with decreasing of lipid peroxide content was closely associated with the protection of grains by maintaining membrane integrity during rice grain filling. The results indicated that temporal dynamics of H2O2 metabolic machinery was strongly up-regulated especially at the mid-milky stage.     

菜用大豆种子劣变与生理生化变化的关系

本文以菜用大豆种子为试材,研究了不同活力种子发生的一些生理生化变化。结果表明,随着种子劣变,细胞膜结构和功能受到损伤,浸泡液电导率增加;当种子丧失生活力后,细胞膜损伤严重,并失去修复能力,内含物大量外渗。高活力种子吸胀葫发过程中呼吸代谢旺盛,而低活力种子呼吸强度较弱。当种子失去生活力后,胚轴中测不出过氧化物酶的活性,胚轴、子叶过氧化物酶同工酶谱带减少,峰高降低;胚轴酯酶同工酶谱带减少,峰高降低,而子叶酯酶同工酶很少发生变化。     

Medium Light and Medium Roast Paper-Filtered Coffee Increased Antioxidant Capacity in Healthy Volunteers: Results of a Randomized Trial

We compared the effects of medium light roast (MLR) and medium roast (MR) paper-filtered coffee on antioxidant capacity and lipid peroxidation in healthy volunteers. In a randomized crossover study, 20 volunteers consumed 482?±?61?ml/day of MLR or MR for four weeks. Plasma total antioxidant status (TAS), oxygen radical absorbance capacity (ORAC), oxidized LDL and 8-epi-prostaglandin F2α, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity were measured at baseline and after the interventions. MLR had higher chlorogenic acids-(CGA; 334?mg/150?mL) and less caffeine (231?mg/150?ml) than MR had (210 and 244?mg/150?ml, respectively). MLR also had fewer Maillard reaction products (MRP) than MR had. Compared with baseline, subjects had an increase of 21 and 26?% in TAS, 13 and 13?% in CAT, 52 and 75?% in SOD, and 62 and 49?% in GPx after MLR and MR consumption (P?相似文献   

Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells

Pregnane X receptor (PXR) has been reported to regulate the expression of drug-metabolizing enzymes, such as the cytochrome P450 3A (CYP3A) family and transporters, such as multiple drug resistance 1 (MDR1). Fucoxanthin, the major carotenoid in brown sea algae, is a putative chemopreventive agent. In this study, we determined whether fucoxanthin could overcome drug resistance through attenuation of rifampin-induced CYP3A4 and MDR1 gene expression by PXR-mediated pathways in HepG2 hepatoma cells. We found that fucoxanthin (1-10 μM) significantly attenuated rifampin (20 μM)-induced CYP3A4, MDR1 mRNA and CYP3A4 protein expression at 24 h of incubation. Mechanistically, fucoxanthin strongly attenuated the PXR-mediated CYP3A4 promoter activity in HepG2 cells. In addition, fucoxanthin attenuated constitutive androstane receptor (CAR)- and rPXR-mediated CYP3A4 promoter activity in this cell line. Using the mammalian two-hybrid assay, we found that fucoxanthin significantly decreased the interaction between PXR and SRC-1, a PXR co-activator. Thus, fucoxanthin can decrease rifampin-induced CYP3A4 and MDR1 expression through attenuation of PXR-mediated CYP3A4 promoter activation and interaction between PXR and co-activator. These findings could lead to potentially important new therapeutic and dietary approaches to reduce the frequency of adverse drug reactions.     

Antioxidant Effect of Dietary Supplement Withania somnifera L. Reduce Blood Glucose Levels in Alloxan-Induced Diabetic Rats

The phenolic compounds and flavonoids were determined from the extracts of Withania somnifera root (WSREt) and leaf (WSLEt). The WSREt has 28.26 mg/g total phenolic compounds and 17.32 mg/g flavonoids, whereas WSLEt has 5.4 mg/g total phenolic compounds and 5.1 mg/g flavonoids. The WSREt, WSLEt and glibenclamide were orally administered daily to diabetic rats for 8 weeks. After the treatment, the levels of urine sugar, blood glucose, liver glycogen, and antioxidants like vitamin C and E in plasma and superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in liver, kidney and heart were determined. Diabetic rats showed a significant (p < 0.05) elevation in glucose and TBARS and a significant (p < 0.05) reduction in glycogen, vitamin C and E, SOD, CAT, GPx, GST, and GSH levels when compared to normal control rats. Administration of WSREt, WSLEt and glibenclamide to diabetic rats restored the levels to normal. In the light of aforesaid facts, it is suggested that the presence of phenolic compounds including flavonoids in W. somnifera root and leaf extracts and their antioxidant activity may play a vital role in reduction of blood glucose level in alloxan-induced diabetic rats.     

大豆胞囊线虫热激蛋白基因Hsp70的克隆与原核表达

采用RT-PCR技术结合基因组步移技术,从大豆胞囊线虫(Heterodera glycines)中克隆了热激蛋白70基因(Hsp70)的全长cDNA序列(Hg-Hsp-70),全长1 953 bp,GenBank登录号为FJ816100.1。碱基序列分析结果表明,该序列含有9个外显子与8个内含子,与其它线虫具有较高的同源性。氨基酸序列分析表明,该基因编码650个氨基酸,相对分子量为70.7 kD,具有2个Hsp70基因家族的签名序列,与其它线虫的该基因氨基酸序列具有很高的同源性。构建了原核表达载体Hsp70pEASY-E1,采用IPTG诱导蛋白表达,SDS-PAGE电泳结果表明,当IPTG终浓度为0.2～1.2 mmol.L-1时均能显著诱导表达;以终浓度0.8 mmol.L-1的IPTG诱导5 h蛋白表达量达到最大值。     

First Report of a Peroxiredoxin Homologue in Jellyfish: Molecular Cloning,Expression and Functional Characterization of CcPrx4 from Cyanea capillata

We first identified and characterized a novel peroxiredoxin (Prx), designated as CcPrx4, from the cDNA library of the tentacle of the jellyfish Cyanea capillata. The full-length cDNA sequence of CcPrx4 consisted of 884 nucleotides with an open reading frame encoding a mature protein of 247 amino acids. It showed a significant homology to peroxiredoxin 4 (Prx4) with the highly conserved F-motif (⁹³FTFVCPTEI¹⁰¹), hydrophobic region (²¹⁷VCPAGW²²²), ¹⁴⁰GGLG¹⁴³ and ²³⁹YF²⁴⁰, indicating that it should be a new member of the Prx4 family. The deduced CcPrx4 protein had a calculated molecular mass of 27.2 kDa and an estimated isoelectric point of 6.3. Quantitative real-time PCR analysis showed that CcPrx4 mRNA could be detected in all the jellyfish tissues analyzed. CcPrx4 protein was cloned into the expression vector, pET-24a, and expressed in Escherichia coli Rosetta (DE3) pLysS. Recombinant CcPrx4 protein was purified by HisTrap High Performance chelating column chromatography and analyzed for its biological function. The results showed that the purified recombinant CcPrx4 protein manifested the ability to reduce hydrogen peroxide and protect supercoiled DNA from oxidative damage, suggesting that CcPrx4 protein may play an important role in protecting jellyfish from oxidative damage.     

茶多酚对苯并[a]芘致青鳉鱼后代发育畸形的拮抗作用

为了研究茶多酚对苯并[a]芘致日本青鳉鱼后代畸形的拮抗及其可能机理,本研究采用正在产卵的青鳉鱼为模式生物,采用腹腔注射法研究了茶多酚对苯并[a]芘致其后代发育畸形的影响,并用逆转录-实时荧光定量PCR法检测肝脏组织内的CYP酶（CYP1A1、CYP1B、CYP2A、CYP2C、CYP2D、CYP3A）和GST基因（mGST、GST-a）的mRNA表达情况。结果表明,单独注射苯并[a]芘组日本青鳉鱼后代畸形率达到15.13%,显著高于对照;茶多酚拮抗组后代畸形率有所下降,除茶多酚最低剂量组（20μg/g BaP+2μg/g TP）外,其他组与BaP组间均存在显著差异。实时荧光定量PCR结果表明,苯并芘试验组对CYP1A1、CYP1B、CYP2A、CYP2C、CYP2D有轻微诱导,并显著抑制雌鱼mGST和GST-a的表达,同时茶多酚可明显抑制CYP1A1基因和谷胱甘肽-S转移酶基因mGST和GST-a的表达。表明茶多酚的抗畸变机理可能与抑制CYP1A1基因表达以及加速苯并芘代谢有关。     

The Inhibition Effect of the Seaweed Polyphenol, 7-Phloro-Eckol from Ecklonia Cava on Alcohol-Induced Oxidative Stress in HepG2/CYP2E1 Cells

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people’s health, and the incidence of ALD is increasing; therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.     

Brevetoxin and Conotoxin Interactions with Single-Domain Voltage-Gated Sodium Channels from a Diatom and Coccolithophore

The recently characterized single-domain voltage-gated ion channels from eukaryotic protists (EukCats) provide an array of novel channel proteins upon which to test the pharmacology of both clinically and environmentally relevant marine toxins. Here, we examined the effects of the hydrophilic µ-CTx PIIIA and the lipophilic brevetoxins PbTx-2 and PbTx-3 on heterologously expressed EukCat ion channels from a marine diatom and coccolithophore. Surprisingly, none of the toxins inhibited the peak currents evoked by the two EukCats tested. The lack of homology in the outer pore elements of the channel may disrupt the binding of µ-CTx PIIIA, while major structural differences between mammalian sodium channels and the C-terminal domains of the EukCats may diminish interactions with the brevetoxins. However, all three toxins produced significant negative shifts in the voltage dependence of activation and steady state inactivation, suggesting alternative and state-dependent binding conformations that potentially lead to changes in the excitability of the phytoplankton themselves.     

Effects of temperature on copper resistance in daf-21 mutant and Hsp90 expression of Caenorhabditis elegans

To determine the effects of temperature alterations on copper toxicity and stress response in Caenorhabditis elegans, an aquatic acute toxicity test was utilized to combinations of four temperature levels (15, 20, 25, and 30°C) and four copper concentrations (0, 0.013, 0.13, and 1.3 mM). Endpoints used included 24-h median lethal concentrations (LC50) value, and 90-kDa heat shock proteins (Hsp90) induction. Results showed a significant acceleration in the mortality with increasing temperature and depressed expression in Hsp90 of the presence of copper. Data on LC50 revealed that simultaneous exposure to both copper and heat stress (30°C) was severe. In contrast, subdued reactions to copper were observed in adult nematode exposed to low temperature (15°C). We have discovered that daf-21 mutation adults result in decreased Cu²⁺ resistance in a 24 h toxicity assay. Significantly weak expression of Hsp90 in C. elegans was observed at high copper stress as LC50 concentration irrespective of temperatures. These results suggest acclimation temperatures caused variations in copper stress of C. elegans, and Hsp90 expression exhibited greater severity with increasing copper concentration. The present study confirms that temperature effectively confounds copper toxicity and needs to be considered for the accurate prediction and assessment of copper-induced toxicity in nematode.     

Biological Activity and Stability of Aeruginosamides from Cyanobacteria

Aeruginosamides (AEGs) are classified as cyanobactins, ribosomally synthesized peptides with post-translational modifications. They have been identified in cyanobacteria of genera Microcystis, Oscillatoria, and Limnoraphis. In this work, the new data on the in vitro activities of three AEG variants, AEG A, AEG625 and AEG657, and their interactions with metabolic enzymes are reported. Two aeruginosamides, AEG625 and AEG657, decreased the viability of human breast cancer cell line T47D, but neither of the peptides was active against human liver cancer cell line Huh7. AEGs also did not change the expression of MIR92b-3p, but for AEG625, the induction of oxidative stress was observed. In the presence of a liver S9 fraction containing microsomal and cytosolic enzymes, AEG625 and AEG657 showed high stability. In the same assays, quick removal of AEG A was recorded. The peptides had mild activity against three cytochrome P450 enzymes, CYP2C9, CYP2D6 and CYP3A4, but only at the highest concentration used in the study (60 µM). The properties of AEGs, i.e., cytotoxic activity and in vitro interactions with important metabolic enzymes, form a good basis for further studies on their pharmacological potential.