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1.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33537813

RESUMEN

The activation of oxidative stress is a primary cause of chondrocyte apoptosis in osteoarthritis (OA). The 78­kDa glucose­regulated protein (GRP78)/mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated to be linked with the endoplasmic reticulum (ER) and autophagy. Hydrogen sulfide (H2S) has been reported to exert antioxidant effects. The present study investigated oxidative stress levels via 2',7'­dichlorofluorescin diacetate and MitoSOX staining, apoptosis rates via flow cytometry and the expression levels of ER stress­related proteins in GYY4137 (donor of H2S)­treated chondrocytes (CHs). CHs were isolated from the bilateral hip joints of male rats to examine mitochondrial permeability transition pore opening­ and mTOR signaling pathway­related proteins. The results demonstrated that tert­Butyl hydroperoxide (TBHP) increased CH apoptosis, and treatment with GYY4137 ameliorated TBHP­mediated the generation of ROS and CH apoptosis. Moreover, TBHP­treated CHs displayed elevated ER stress sensor expression levels and apoptotic rates; however, the TBHP­induced protein expression levels were decreased following GYY4137 treatment. In the present study, treatment with either GYY4137 or transfection with GRP78 siRNA both suppressed the activation of p­P70S6k and p­mTOR. H2S played an important role in regulating ER stress in TBHP­stimulated CHs. GYY4137 promoted autophagy, which was accompanied by the inhibition of ER stress. On the whole, the present study demonstrates that TBHP­induced oxidative stress stimulates ER interactions and CH apoptosis, which are suppressed by exogenous H2S via modulating the GRP78/mTOR signaling pathway.


Asunto(s)
Condrocitos/metabolismo , Condrocitos/patología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas de Choque Térmico/metabolismo , Sulfuro de Hidrógeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cloroquina/farmacología , Condrocitos/efectos de los fármacos , Citoprotección/efectos de los fármacos , Masculino , Morfolinas/química , Morfolinas/farmacología , Compuestos Organotiofosforados/química , Compuestos Organotiofosforados/farmacología , Peróxidos/farmacología , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
2.
BMC Complement Med Ther ; 21(1): 66, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602182

RESUMEN

BACKGROUND: High glucose (HG)-induced reactive oxygen species (ROS) overproduction impairs angiogenesis that is one pivotal factor of wound healing process. Angiogenesis impairment induces delayed wound healing, whereby it eventually leads to amputation in cases of poorly controlled diabetes with diabetic ulceration. Porcine placenta extract (PPE) is a natural waste product that comprises plenty of bioactive agents including growth factors and antioxidants. It was reported as an effective compound that prevents ROS generation. The goal of this study was to investigate the in vitro effect of PPE on HG-induced ROS-mediated angiogenesis impairment. METHODS: Primary endothelial cells (HUVECs) and endothelial cell line (EA.hy926) were treated with HG in the presence of PPE. The endothelial cells (ECs) viability, intracellular ROS generation, migration, and angiogenesis were determined by MTT assay, DCFDA reagent, wound healing assay, and tube formation assay, respectively. Additionally, the molecular mechanism of PPE on HG-induced angiogenesis impairment was investigated by Western blot. The angiogenic growth factor secretion was also investigated by the sandwich ELISA technique. RESULTS: HG in the presence of PPE significantly decreased intracellular ROS overproduction compared to HG alone. HG in the presence of PPE significantly increased ECs viability, migration, and angiogenesis compared to HG alone by showing recovery of PI3K/Akt/ERK1/2 activation. HG in the presence of PPE also decreased ECs apoptosis compared to HG alone by decreasing p53/Bax/cleaved caspase 9/cleaved caspase 3 levels and increasing Bcl 2 level. CONCLUSION: PPE attenuated HG-induced intracellular ROS overproduction that improved ECs viability, proliferation, migration, and angiogenesis by showing recovery of PI3K/Akt/ERK1/2 activation and inhibition of ECs apoptosis. This study suggests PPE ameliorated HG-induced ROS-mediated angiogenesis impairment, whereby it potentially provides an alternative treatment for diabetic wounds.


Asunto(s)
Productos Biológicos/farmacología , Células Endoteliales/efectos de los fármacos , Glucosa/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Placenta/química , Porcinos , Cicatrización de Heridas/efectos de los fármacos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Productos Biológicos/química , Línea Celular , Movimiento Celular , Supervivencia Celular , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Células Endoteliales/metabolismo , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
3.
BMC Pulm Med ; 21(1): 58, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588817

RESUMEN

BACKGROUND: Hyperoxia downregulates the tight junction (TJ) proteins of the alveolar epithelium and leads to barrier dysfunction. Previous study has showed that STE20/SPS1-related proline/alanine-rich kinase (SPAK) interferes with the intestinal barrier function in mice. The aim of the present study is to explore the association between SPAK and barrier function in the alveolar epithelium after hyperoxic exposure. METHODS: Hyperoxic acute lung injury (HALI) was induced by exposing mice to > 99% oxygen for 64 h. The mice were randomly allotted into four groups comprising two control groups and two hyperoxic groups with and without SPAK knockout. Mouse alveolar MLE-12 cells were cultured in control and hyperoxic conditions with or without SPAK knockdown. Transepithelial electric resistance and transwell monolayer permeability were measured for each group. In-cell western assay was used to screen the possible mechanism of p-SPAK being induced by hyperoxia. RESULTS: Compared with the control group, SPAK knockout mice had a lower protein level in the bronchoalveolar lavage fluid in HALI, which was correlated with a lower extent of TJ disruption according to transmission electron microscopy. Hyperoxia down-regulated claudin-18 in the alveolar epithelium, which was alleviated in SPAK knockout mice. In MLE-12 cells, hyperoxia up-regulated phosphorylated-SPAK by reactive oxygen species (ROS), which was inhibited by indomethacin. Compared with the control group, SPAK knockdown MLE-12 cells had higher transepithelial electrical resistance and lower transwell monolayer permeability after hyperoxic exposure. The expression of claudin-18 was suppressed by hyperoxia, and down-regulation of SPAK restored the expression of claudin-18. The process of SPAK suppressing the expression of claudin-18 and impairing the barrier function was mediated by p38 mitogen-activated protein kinase (MAPK). CONCLUSIONS: Hyperoxia up-regulates the SPAK-p38 MAPK signal pathway by ROS, which disrupts the TJ of the alveolar epithelium by suppressing the expression of claudin-18. The down-regulation of SPAK attenuates this process and protects the alveolar epithelium against the barrier dysfunction induced by hyperoxia.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Células Epiteliales Alveolares/metabolismo , Claudinas/genética , Hiperoxia/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Alveolos Pulmonares/metabolismo , Uniones Estrechas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Lesión Pulmonar Aguda/patología , Células Epiteliales Alveolares/ultraestructura , Animales , Líquido del Lavado Bronquioalveolar/química , Claudinas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Hiperoxia/patología , Ratones , Ratones Noqueados , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Permeabilidad , Proteínas Serina-Treonina Quinasas/metabolismo , Alveolos Pulmonares/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Uniones Estrechas/ultraestructura
4.
Nat Commun ; 12(1): 869, 2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33558521

RESUMEN

The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank-Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Here we show that the mechanically activated Piezo1 channel converts mechanical stretch of cardiomyocytes into Ca2+ and reactive oxygen species (ROS) signaling, which critically determines the mechanical activity of the heart. Either cardiac-specific knockout or overexpression of Piezo1 in mice results in defective Ca2+ and ROS signaling and the development of cardiomyopathy, demonstrating a homeostatic role of Piezo1. Piezo1 is pathologically upregulated in both mouse and human diseased hearts via an autonomic response of cardiomyocytes. Thus, Piezo1 serves as a key cardiac mechanotransducer for initiating mechano-chemo transduction and consequently maintaining normal heart function, and might represent a novel therapeutic target for treating human heart diseases.


Asunto(s)
Canales Iónicos/metabolismo , Mecanotransducción Celular , Miocardio/metabolismo , Animales , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatología , Calcio/metabolismo , Señalización del Calcio , Cardiomiopatías/metabolismo , Cardiomiopatías/fisiopatología , Eliminación de Gen , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Pruebas de Función Cardíaca , Homeostasis , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Especificidad de Órganos , Pirazinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tiadiazoles/metabolismo , Regulación hacia Arriba
5.
Adv Exp Med Biol ; 1275: 165-193, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33539016

RESUMEN

Toxicity of metal nanoparticles (NPs) are closely associated with increasing intracellular reactive oxygen species (ROS) and the levels of pro-inflammatory mediators. However, NP interactions and surface complexation reactions alter the original toxicity of individual NPs. To date, toxicity studies on NPs have mostly been focused on individual NPs instead of the combination of several species. It is expected that the amount of industrial and highway-acquired NPs released into the environment will further increase in the near future. This raises the possibility that various types of NPs could be found in the same medium, thereby, the adverse effects of each NP either could be potentiated, inhibited or remain unaffected by the presence of the other NPs. After uptake of NPs into the human body from various routes, protein kinases pathways mediate their toxicities. In this context, family of mitogen-activated protein kinases (MAPKs) is mostly efficient. Despite each NP activates almost the same metabolic pathways, the toxicity induced by a single type of NP is different than the case of co-exposure to the combined NPs. The scantiness of toxicological data on NPs combinations displays difficulties to determine, if there is any risk associated with exposure to combined nanomaterials. Currently, in addition to mathematical analysis (Response surface methodology; RSM), the quantitative-structure-activity relationship (QSAR) is used to estimate the toxicity of various metal oxide NPs based on their physicochemical properties and levels applied. In this chapter, it is discussed whether the coexistence of multiple metal NPs alter the original toxicity of individual NP. Additionally, in the part of "Toxicity of diesel emission/exhaust particles (DEP)", the known individual toxicity of metal NPs within the DEP is compared with the data regarding toxicity of total DEP mixture.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Humanos , Nanopartículas del Metal/toxicidad , Proteínas Quinasas Activadas por Mitógenos , Nanopartículas/toxicidad , Óxidos , Especies Reactivas de Oxígeno , Titanio
6.
Med Sci Monit ; 27: e926492, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33563887

RESUMEN

BACKGROUND The aim of this study was to evaluate the potential role of dual oxidase 1 (DUOX1) in wound healing. MATERIAL AND METHODS Primary fibroblasts were isolated from wound granulation tissue. Fibroblasts cell lines were established using DUOX1 overexpression and interference. Cell proliferation and reactive oxygen species (ROS) production were measured and compared among the groups. RESULTS DUOX1 expression was highest in the slow-healing tissues (P<0.05). Knockdown of DUOX1 significantly increased cell proliferation and inhibited ROS production and cell apoptosis (P<0.01). Moreover, expression of malondialdehyde (MDA) was significantly reduced, while expression of superoxide dismutase (SOD) expression was significantly increased (P<0.01). In addition, DUOX1 silencing significantly upregulated collagen I, collagen III, and NF-kappaB protein levels in the cytoplasm, and inhibited the protein levels of P21, P16, and NF-kappaB in the nucleus (P<0.01). Overexpression of DUOX1 caused a reverse reaction mediated by knockdown of DUOX1. When DUOX1-overexpressing cells were treated with the ROS inhibitor N-acetyl-L-cysteine (NAC), the protein levels that were increased by DUOX1 overexpression were reversed. CONCLUSIONS These results suggest that knockdown of DUOX1 significantly benefits wound healing, likely by the regulation of oxidative stress via NF-kappaB pathway activation.


Asunto(s)
Oxidasas Duales/metabolismo , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas/fisiología , Acetilcisteína/farmacología , Adulto , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Células Cultivadas , Oxidasas Duales/genética , Femenino , Fibroblastos , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Cultivo Primario de Células , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Superóxido Dismutasa/metabolismo , Cicatrización de Heridas/efectos de los fármacos
7.
Yakugaku Zasshi ; 141(1): 111-124, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33390438

RESUMEN

Phototoxicity is a toxic response elicited by topically applied or systemically administered photoreactive chemicals after exposure to light and can be broadly categorized into photoirritation, photoallergy, photogenotoxicity, and photocarcinogenicity. The need in the 21st century for accurate evaluation of photosafety has led to the publication of a number of guidelines from government agencies in Europe and the U.S.A. as well as the Organisation for Economic Co-operation and Development (OECD). In this review, we first discuss the mechanisms of phototoxicity and how they can be evaluated. We then discuss the state of the art and challenges now faced in photosafety evaluation of pharmaceuticals and cosmetics. Additionally, we describe the latest developments in OECD test guidelines (TG) for assessing photosafety, including revisions to the in vitro 3T3 neutral red uptake (NRU) phototoxicity test (TG 432) and the newly adopted reactive oxigen species (ROS) assay (TG 495). We will emphasize the importance of selecting the most appropriate means of evaluation with reference to the latest guidelines and other legal criteria for conducting photosafety evaluation.


Asunto(s)
Dermatitis Fototóxica/diagnóstico , Dermatitis Fototóxica/etiología , Luz/efectos adversos , Rojo Neutro/toxicidad , Células 3T3 , Animales , Células Cultivadas , Humanos , Ratones , Especies Reactivas de Oxígeno/análisis , Seguridad , Pruebas de Toxicidad/métodos
8.
Yakugaku Zasshi ; 141(1): 135-142, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33390440

RESUMEN

Environmental microorganisms can cause several infections in humans, especially in compromised hosts. Since there are many compromised hosts in a hospital setting, it is important to control environmental pathogens in such scenarios. To disinfect the environment, photocatalysts that produce reactive oxygen in response to light have attracted attention. In the present study, the effects of a visible-light-driven antimicrobial photocatalyst, silver (I) iodide and benzalkonium complex, on bacteria, viruses, and fungi were evaluated in vitro. In addition, uncoated panels and panels coated with the photocatalyst were set up at 11 points in a university campus for 6 months, and the adherent bacteria and fungi were measured. Bacteria, bacterial spores, viruses, and fungi were completely inactivated within 45 min on the photocatalyst-coated surface exposed to approximately 700-lux fluorescent light. In the university setting, there were fewer viable adherent bacteria and fungi on the coated plates. Our findings indicate that the silver (I) iodide and benzalkonium complex photocatalyst can decrease environmental bacteria in vitro and in actual environmental settings, and thus highlight its potential in controlling and disinfecting environmental pathogens.


Asunto(s)
Compuestos de Benzalconio , Desinfección/métodos , Microbiología Ambiental , Fluorescencia , Control de Infecciones/métodos , Yoduros , Luz , Compuestos de Plata , Bacterias/efectos de los fármacos , Compuestos de Benzalconio/farmacología , Hongos/efectos de los fármacos , Yoduros/farmacología , Especies Reactivas de Oxígeno/farmacología , Compuestos de Plata/farmacología , Inactivación de Virus/efectos de los fármacos
9.
Chemosphere ; 269: 129337, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33387793

RESUMEN

Acetaminophen (ACT) and phenacetin (PNT) removal during light-emitting diode (LED)-UV photolysis of persulfate (PS) was evaluated with a typical wavelength of 365 nm. Decay of PNT and ACT in pH ranges of 5.5-8.5 followed pseudo-first order kinetics. Maximum pseudo-first order rate constants (kobs) of ACT and PNT decomposition of 1.8 × 10-1 and 1.2 × 10-1 min-1, respectively, were obtained at pH 8.5. Hydroxyl radicals (·OH), sulfate radicals (SO4·-), superoxide radicals (O2-·), and singlet oxygen (1O2) were determined in-situ electron paramagnetic resonance (EPR) and alcohol scavenging tests. The average contributions of ·OH and SO4·- were 23.5% and 53.0% for PNT removal, and 15.9% and 53.0% for ACT removal at pH ranges of 5.5-8.5. In samples subjected to chlorination after LED-UV365/PS pre-oxidation, a relatively small total concentration of five halogenated disinfection by-products (DBPs) was obtained of 90.9 µg L-1 (pH 5.5) and 126.7 µg L-1 (pH 7.0), which is 58.5% and 30.2% lower than that in system without LED-UV365/PS pre-oxidation. Meanwhile, a higher maximum value of total DBP concentration was obtained at pH 8.5 (445.6 µg L-1) following LED-UV365/PS pre-oxidation. The results of economy evaluation showed that UV365 was more cost-effective in application for organic contaminant removal compared with UV254.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Acetaminofén , Cinética , Oxidación-Reducción , Fenacetina , Fotólisis , Especies Reactivas de Oxígeno , Rayos Ultravioleta , Contaminantes Químicos del Agua/análisis
10.
Mol Cell ; 81(3): 629-637.e5, 2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33400924

RESUMEN

As a master regulator of metabolism, AMP-activated protein kinase (AMPK) is activated upon energy and glucose shortage but suppressed upon overnutrition. Exaggerated negative regulation of AMPK signaling by nutrient overload plays a crucial role in metabolic diseases. However, the mechanism underlying the negative regulation is poorly understood. Here, we demonstrate that high glucose represses AMPK signaling via MG53 (also called TRIM72) E3-ubiquitin-ligase-mediated AMPKα degradation and deactivation. Specifically, high-glucose-stimulated reactive oxygen species (ROS) signals AKT to phosphorylate AMPKα at S485/491, which facilitates the recruitment of MG53 and the subsequent ubiquitination and degradation of AMPKα. In addition, high glucose deactivates AMPK by ROS-dependent suppression of phosphorylation of AMPKα at T172. These findings not only delineate the mechanism underlying the impairment of AMPK signaling in overnutrition-related diseases but also highlight the significance of keeping the yin-yang balance of AMPK signaling in the maintenance of metabolic homeostasis.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus/enzimología , Glucosa/farmacología , Proteínas de la Membrana/metabolismo , Músculo Esquelético/efectos de los fármacos , Obesidad/enzimología , Proteínas Quinasas Activadas por AMP/genética , Animales , Glucemia/metabolismo , Diabetes Mellitus/sangre , Diabetes Mellitus/genética , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Macaca mulatta , Masculino , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Músculo Esquelético/enzimología , Obesidad/sangre , Obesidad/genética , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteolisis , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Ubiquitinación
11.
Toxicol Lett ; 340: 33-42, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33421550

RESUMEN

Toxic and volatile chemicals are widely used in household products and previously used as warfare agents, causing a public health threat worldwide. This study aimed to evaluate the extent of injury and mechanisms of acrolein toxicity in the cornea. Primary human corneal stromal fibroblasts cultures (hCSFs) from human donor cornea were cultured and exposed to acrolein toxicity with -/+ N-acetylcysteine (NAC) to study the mode of action in the presence of Buthionine sulphoximine (BSO). PrestoBlue and MTT assays were used to optimize acrolein, NAC, and BSO doses for hCSFs. Cell-based assays and qRT-PCR analyses were performed to understand the acrolein toxicity and mechanisms. Acrolein exposure leads to an increased reactive oxygen species (ROS), compromised glutathione (GSH) levels, and mitochondrial dysfunction. The TUNEL and caspase assays showed that acrolein caused cell death in hCSFs. These deleterious effects can be mitigated using NAC in hCSFs, suggesting that GSH can be a potential target for acrolein toxicity in the cornea.


Asunto(s)
Acroleína/toxicidad , Córnea/citología , Fibroblastos/efectos de los fármacos , Glutatión/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 7/genética , Caspasa 7/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citoprotección/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Peroxidación de Lípido , Lípidos/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo , Especies Reactivas de Oxígeno
12.
Ecotoxicol Environ Saf ; 208: 111708, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396039

RESUMEN

In a laboratory based study, Salvinia natans L. was pre-treated with reduced glutathione (GSH) following transfer under 2, 4-Dicholro phenoxy acetic acid (2,4-D), peroxide (H2O2), dark and irradiation. Plants recorded 2, 4-D bio-accumulation and tolerance maximally under 500 µM following absorption kinetics modulated with GSH in changes of relative water content (20.98%), growth rate (3.04%) and net assimilation rate (1.3 fold) over control. GSH pre-treatment minimized the oxidative revelation with reactive oxygen species (ROS) by 5.55% decrease under 2, 4-D and 1.3, 1.2, 0.8 fold increase through the other stresses. Apoplastic NADPH-oxidase expression was moderated by GSH with 11.76% less over the control. Also the activity of alcohol dehydrogenase and glutathione-S-transferase had their altered values by 1.5 and 9.0 fold increases respectively and may serve as biomarkers. The oxidized:reduced glutathione was positively correlated with glutathione-peroxidase (r=+0.99) and negatively with glutathione reductase (r=-0.04). The induced activities sustained oxidized:reduced GSH pool by 1.09 fold and had varied polymorphic gene expression under 2, 4-D and allied stresses. This study may be relevant to consider Salvinia as a potent weed species remediating 2, 4-D toxicity in soil with its wider hyper-accumulating efficiency. The cellular responses in tolerance to oxidative stress and thereby, induced physiological attributes may opt for selection pressures in other weed flora for broader aspects of phytoremediation against xenobiotics like 2, 4-D.


Asunto(s)
Ácido 2,4-Diclorofenoxiacético/metabolismo , Helechos/metabolismo , Glutatión/metabolismo , Estrés Oxidativo , Biodegradación Ambiental/efectos de la radiación , Biomarcadores/metabolismo , Oscuridad , Glutatión/farmacología , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Luz , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Proteínas de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 57-63, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33474890

RESUMEN

Metabolic aberrance is one of the hallmarks of cancer. The metabolic patterns in cancer cells are well reprogrammed to provide building blocks and energy for their sustained growth. During tumor metabolic reprogramming, reactive oxygen species (ROS) are generated and the antioxidant systems are activated. High levels of ROS lead to oxidative damage and even cell death, whereas ROS at low levels act as second messenger to regulate many signaling pathways. Recently, with the revisiting of oxidative stress, it has been found that ROS can directly mediate the redox modifications of proteins, resulting in protein conformational and functional alterations. However, only a very small portion of metabolic enzymes, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and PKM2, etc., has been reported to undergo redox modifications. Whether other metabolic enzymes are regulated by redox modifications and thus exhibit critical functions remain largely unknown. Moreover, the specific spatio-temporal targeting of redox modifications of metabolic enzymes, as well as overcoming the existed redox and metabolic adaptation, are key points to be solved. Here, we will review the reported redox modification patterns of metabolic enzymes, the involved regulatory mechanisms and their roles in tumorigenesis and tumor progress. In addition, we will discuss the future therapeutic strategies targeting redox modifications of metabolic enzymes for tumor treatment.


Asunto(s)
Neoplasias , Estrés Oxidativo , Antioxidantes , Humanos , Oxidación-Reducción , Especies Reactivas de Oxígeno
14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(2): 105-112, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33504415

RESUMEN

Objective To investigate the effect of oxidative stress preconditioning on the oxidative stress-induced damage of bone marrow mesenchymal stem cells (BMSCs). Methods BMSCs were isolated and cultured by density gradient centrifugation combined with adherence method. The cells were divided into three groups: control group (control medium), oxidative damage group (treated with 1000 µmol/L H2O2 for 24 hours), and preconditioning group (preincubated with 50 µmol/L H2O2 for 8 hours before treatment with 1000 µmol/L H2O2 for 24 hours). DCFH-DA staining was used to analyze the level of reactive oxygen species (ROS). Mitochondrial membrane potential was measured by JC-1 staining. DNA damage was detected by TUNEL. Malondialdehyde (MDA) content was detected by thiobarbituric acid (TBA) method, and superoxide dismutase (SOD) activity was detected by water soluble tetrazolium-1 (WST-1) assay. CCK-8 assay was used to detect cell viability and flow cytometry to detect cell apoptosis. Results Compared with the oxidative damage group, the preconditioning group had reduced ROS level, reduced DNA damage, higher mitochondrial membrane potential, significantly decreased MDA content, increased SOD activity, increased cell viability, and significantly decreased apoptosis. Conclusion Oxidative stress preconditioning can enhance the anti-oxidative stress ability of BMSCs and promote its survival under oxidative stress.


Asunto(s)
Células Madre Mesenquimatosas , Apoptosis , Células de la Médula Ósea , Peróxido de Hidrógeno/toxicidad , Malondialdehído , Estrés Oxidativo , Especies Reactivas de Oxígeno
15.
Environ Pollut ; 272: 116413, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33422762

RESUMEN

Paraquat (PQ) is one of the most widely used herbicides in the world due to its excellent weed control effects. Accumulating evidence has revealed that long-term exposure to PQ can significantly increase the risk of Parkinson's disease (PD). However, the underlying molecular mechanisms are yet to be fully understood. Hence, we investigated the potential role of reactive oxygen species (ROS) and dynamin-related protein 1 (DRP1) in PQ-induced mitophagy, aiming to elaborate on possible molecular mechanisms involved in PQ-triggered neurotoxicity. Our results showed that ROS were increased, mitochondrial membrane potential was decreased at 100, 200, and 300 µM PQ concentrations, and autophagy pathways were activated at a concentration of 100 µM in neuronal cells. In addition, excessive mitophagy was observed in neurons exposed to 300 µM PQ for 24 h. Then, ROS-mediated mitochondrial fission was found to contribute to PQ-induced excessive mitophagy. Moreover, all aforementioned changes were significantly ameliorated by mdivi-1. Thus, our findings provide a novel neurotoxic mechanism and reveal the DRP1-mitochondrial fission pathway as a potential target for treatments of PQ-induced excessive mitophagy, serving as an alternative target for the prevention and treatment of Parkinson's disease. Because harmful substances are transmitted and enriched in the food chain, the toxic effect of environmental paraquat is nonnegligible, and more investigations are needed.


Asunto(s)
Herbicidas , Paraquat , Herbicidas/toxicidad , Dinámicas Mitocondriales , Mitofagia , Neuronas , Paraquat/toxicidad , Especies Reactivas de Oxígeno
16.
Environ Pollut ; 272: 116403, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33433347

RESUMEN

Cadmium (Cd) and excess molybdenum (Mo) are harmful to animals, but the combined nephrotoxic mechanism of Cd and Mo in duck remains poorly elucidated. To assess joint effects of Cd and Mo on pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells, cells were cultured with 3CdSO4·8H2O (4.0 µM), (NH4)6Mo7O24·4H2O (500.0 µM), MCC950 (10.0 µM), BHA (100.0 µM) and combination of Cd and Mo or Cd, Mo and MCC950 or Cd, Mo and BHA for 12 h, and the joint cytotoxicity was explored. The results manifested that toxicity of non-equitoxic binary mixtures of Mo and Cd exhibited synergic interaction. Mo or/and Cd elevated ROS level, PTEN mRNA and protein levels, and decreased PI3K, AKT and p-AKT expression levels. Simultaneously, Mo or/and Cd upregulated ASC, NLRP3, NEK7, Caspase-1, GSDMA, GSDME, IL-18 and IL-1ß mRNA levels and Caspase-1 p20, NLRP3, ASC, GSDMD protein levels, increased the percentage of pyroptotic cells, LDH, NO, IL-18 and IL-1ß releases as well as relative conductivity. Moreover, NLRP3 inhibitor MCC950 and ROS scavenger BHA could ameliorate the above changed factors induced by Mo and Cd co-exposure. Collectively, our results reveal that combination of Mo and Cd synergistically cause oxidative stress and trigger pyroptosis via ROS/PTEN/PI3K/AKT axis in duck tubular epithelial cells.


Asunto(s)
Cadmio , Molibdeno , Animales , Cadmio/toxicidad , Patos , Células Epiteliales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Piroptosis , Especies Reactivas de Oxígeno
17.
Aquat Toxicol ; 231: 105739, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33434705

RESUMEN

Cadmium (Cd) with no known functional role in any life-form has myriad of harmful effects. The present study was designed to elucidate the mechanism of Cd-induced oxystress generation and its impact on antioxidant and apoptosis signaling pathways in head kidney macrophage (HKM) of Channa punctatus Bloch. Fish were sampled and acclimatized with one group treated with cadmium chloride (CdCl2) (1.96 mg/L) and another as untreated control group, both kept under observation for 7 days. Exposure to Cd caused ultrastructural changes along with reduced head kidney somatic index (HKSI). Significantly increased levels of reactive oxygen species (ROS), respiratory burst activity, lipid peroxidation, DNA fragmentation and superoxide dismutase were found in the HKM from the treated group as compared to control. In contrast, antioxidant enzymes like catalase and reduced glutathione activity decreased in the Cd exposed group. The suppressed antioxidant activity was further confirmed and corroborated from the altered expression of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2) genes, the major player of antioxidant pathway. Cd induced alteration in Nrf2-Keap1 signaling pathway was also validated by the diminished levels of Nrf2 dependent expression of protein like heme oxygenase-1 (HO-1). The flow cytometry analysis supported the event of apoptosis in Cd exposed group as compared to control, which was further confirmed by the upregulated expression of caspase-3, caspase-8, caspase-9, TNF-α and p53 genes from the real-time gene expression study. In addition, altered protein level of cytochrome C validates the incidence of apoptosis. Altogether, our results demonstrate that exposure to Cd caused oxidative stress in HKM of Channa punctatus Bloch. by compromising the antioxidant enzyme activities via the down regulation of expression of genes related to antioxidant signaling pathway besides encouraging apoptosis via both mitochondrial and death receptor pathway.


Asunto(s)
Apoptosis , Cadmio/toxicidad , Peces/metabolismo , Riñón Cefálico/citología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Macrófagos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/ultraestructura , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Receptores de Muerte Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Contaminantes Químicos del Agua/toxicidad
18.
Sci Total Environ ; 765: 144630, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33385810

RESUMEN

In this study, the photogeneration of OH and 1O2 and the degradation mechanism of organic pollutants in biochar suspension under the simulated solar light irradiations were investigated. Biochar derived from rice husk with 550 °C of charring temperature (R550) was selected to degrade benzoic acid. It was found that 10 g/L of R550 could degrade 78.7% of benzoic acid within 360 min at pH 3, and the degradation efficiency was promoted to 95.2% as ultraviolet (UV) presented. By checking the production of p-hydroxybenzoic acid, UV accelerated the production of OH, which was confirmed by the enhanced degradation efficiency of 59.2% caused by the evaluated OH as UV appeared. The furfuryl alcohol loss in the R550 suspension under light irradiations testified to the production of 1O2, which contributed to 9.3% of benzoic acid degradation. Oxidization treatment using gradient concentrations of H2O2 was employed to enhance the ageing process of biochar. As the ageing processed, the biochar possessed a declined performance towards OH production from O2 activation and the radical degradation of organic pollutants. As a contrast, the evaluated content of 1O2 and enhanced non-radical degradation of organic pollutants was reached as UV presented. The further study indicated that phenolic hydroxyl groups on biochar facilitated the production of OH via the electron transfer, and quinone like structures (C=O) on biochar boosted the generation of 1O2 via the energy transfer. Moreover, upon eliminating the BA degradation, persistent free radicals were formed on biochar, which was enhanced owing to the presence of UV.


Asunto(s)
Ácido Benzoico , Contaminantes Químicos del Agua , Carbón Orgánico , Composición Familiar , Peróxido de Hidrógeno , Oxidación-Reducción , Especies Reactivas de Oxígeno
19.
Int J Nanomedicine ; 16: 471-480, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33500617

RESUMEN

Background: Doxil® (PEGylated liposomal doxorubicin, PLD) has been widely used in cancer treatment due to its excellent therapeutic efficacy, but it can simultaneously cause severe adverse effects such as hand-foot syndrome (HFS). To date, the pathophysiologic mechanism of HFS development induced by PLD administration has not been well understood. Materials and Methods: The histological features of skin lesion in PLD-induced HFS model were characterized by hematoxylin and eosin (H&E) staining and picrosirius red staining, and the induction of inflammation and apoptosis in the epidermal layer was detected by immunohistochemical and TUNEL staining. Moreover, the generation of reactive oxygen species (ROS) was determined to elucidate the potential mechanism of skin lesion in the development of HFS. Results: The administration of PLD has been demonstrated to induce the histological damage of skin tissues including the destruction of collagen fibers and the induction of severe inflammation and apoptosis of epidermal cells. The mechanism was probably attributed to the accumulation of PLD in the skin tissues during the long-term circulation and further the induction of ROS to cause the oxidative damage of keratinocytes owing to the sustained release of doxorubicin from PLD. Conclusion: The ROS generation induced by the administration of PLD has been identified to be a crucial factor in the development of HFS, which could be used as a potential therapeutic target to alleviate the HFS symptom of PLD administration.


Asunto(s)
Apoptosis , Doxorrubicina/análogos & derivados , Síndrome Mano-Pie/etiología , Síndrome Mano-Pie/patología , Inflamación/patología , Polietilenglicoles/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Inflamación/tratamiento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Queratinocitos/efectos de los fármacos , Polietilenglicoles/administración & dosificación , Ratas Wistar , Piel/patología
20.
Ecotoxicol Environ Saf ; 211: 111928, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33476845

RESUMEN

The chloroacetanilides are among the most commonly used herbicides worldwide, which contaminate aquatic environments and affect aquatic phototrophs. Their sub-lethal toxicity has been evaluated using freshwater algae; however, the modes of cellular toxicity and levels of toxicity to marine organisms are not fully understood. In the present study, we assessed the cellular and molecular effects of chloroacetanilides on marine phototrophs using the dinoflagellate Prorocentrum minimum and the herbicide metazachlor (MZC). The MZC treatment led to a considerable reduction in cell number and pigment, and the EC50 of MZC was calculated to be 0.647 mg/L. The photosynthetic parameters, Fv/Fm and chlorophyll fluorescence significantly decreased with MZC exposure time in a dose-dependent manner. In addition, MZC significantly induced photosynthesis genes, including PmpsbA, PmpsaA, and PmatpB, and the antioxidant PmGST, but not PmKatG. These findings were well matched to reactive oxygen species (ROS) production in MZC-treated cells. Interestingly, we observed inflated vacuoles, undivided chloroplasts, and breakdown of thylakoid membranes in MZC-treated cells. These results support the hypothesis that MZC severely damages chloroplasts, resulting in dysfunction of the dinoflagellate photosynthesis and possibly marine phototrophs in the environment.


Asunto(s)
Acetamidas/toxicidad , Dinoflagelados/fisiología , Herbicidas/toxicidad , Fotosíntesis/efectos de los fármacos , Organismos Acuáticos/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Dinoflagelados/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tilacoides/metabolismo
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