scholarly journals IDENTIFICATION OF OXIDATIVE STRESS-RELATED PROTEINS FOR PREDICTIVE SCREENING OF HEPATOTOXICITY USING A PROTEOMIC APPROACH

2005 ◽  
Vol 30 (3) ◽  
pp. 213-227 ◽  
Author(s):  
Toshinori YAMAMOTO ◽  
Rie KIKKAWA ◽  
Hiroshi YAMADA ◽  
Ikuo HORII
Keyword(s):  
Oxidative Stress ◽  
Proteomic Approach ◽  
Related Proteins

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

scholarly journals Fucoidan Alleviates Acetaminophen-Induced Hepatotoxicity via Oxidative Stress Inhibition and Nrf2 Translocation

2018 ◽  
Vol 19 (12) ◽  
pp. 4050 ◽  
Author(s):  
Yu-qin Wang ◽  
Jin-ge Wei ◽  
Meng-jue Tu ◽  
Jian-guo Gu ◽  
Wei Zhang
Keyword(s):  
Oxidative Stress ◽  
Serum Levels ◽  
Sulfated Polysaccharide ◽  
Intragastric Administration ◽  
Related Factor ◽  
Cell Nuclei ◽  
Brown Seaweeds ◽  
Wide Range ◽  
Related Proteins ◽  
Apap Hepatotoxicity

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress.

scholarly journals Galangin Alleviates Liver Ischemia-Reperfusion Injury in a Rat Model by Mediating the PI3K/AKT Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1354-1363 ◽  
Author(s):  
Yang Li ◽  
Liquan Tong ◽  
Jingyan Zhang ◽  
Yafeng Zhang ◽  
Feng  Zhang
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Hepatic Duct ◽  
Ischemia Reperfusion ◽  
Trauma Surgery ◽  
Liver Ischemia ◽  
Western Blots ◽  
Phosphorylated Akt ◽  
Related Proteins

Background/Aims: Liver ischemia-reperfusion (I/R) injury is a pathological process that often occurs during liver and trauma surgery. There are numerous causes of liver I/R injury, but the mechanism is unknown. Galangin (GA) is a flavonoid, a polyphenolic compound widely distributed in medicinal herbs that has anti-inflammatory, antioxidant, and antitumor activity. This study evaluated the protective effect of GA on hepatic I/R injury. Methods: An I/R model was created in male Wistar rats by clamping the hepatoportal vein, hepatic artery and hepatic duct for 30 min followed by reperfusion for 2 h. A hypoxia/restoration (H/R) model was established in buffalo rat liver (BRL) cells by hypoxia for 4 h followed by normoxic conditions for 10 h. The extent of liver injury was assayed by serum ALT/AST, hepatic histology, and MPO activity. Oxidative stress was assayed by serum superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA). Expression of apoptosis-related proteins in BRL cells was assayed in western blots. Expression of AKT and p-AKT proteins in vivo and vitro were assayed in western blots. Results: GA significantly decreased ALT/AST expression, reversed changes in oxidative stress markers induced by I/R, and mediated caspase-3 activity expression of apoptosis-related proteins in vivo and in vitro. Methylthiazol tetrazolium (MTT) assay, flow cytometry, and Hoechst 33258 staining confirmed that GA inhibited apoptosis of BRL cells. GA also increased the expression of phosphorylated AKT after H/R. Conclusion: GA reduced liver I/R injury both in vivo and vitro and inhibited BRL cell apoptosis. PI3K/AKT signaling have been involved. GA may protect against liver I/R and be a potential therapeutic candidate.

scholarly journals Tucum-do-cerrado (Bactris setosa Mart.) modulates oxidative stress, inflammation, and apoptosis-related proteins in rats treated with azoxymethane

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206670
Author(s):  
Natália A. Campos ◽  
Marcela S. B. da Cunha ◽  
Sandra F. Arruda
Keyword(s):  
Oxidative Stress ◽  
Related Proteins

scholarly journals Glycyrrhizic acid ameliorates submandibular gland oxidative stress, autophagy and vascular dysfunction in rat model of type 1 diabetes

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Saad Mohamed Asseri ◽  
Nehal M. Elsherbiny ◽  
Mohamed El-Sherbiny ◽  
Iman O. Sherif ◽  
Alsamman M. Alsamman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Glycyrrhizic Acid ◽  
Type I Diabetes ◽  
Vascular Dysfunction ◽  
Type I ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Ameliorative Effect ◽  
Related Proteins

AbstractThe burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). The present study aims to investigate the potential ameliorative effect of glycyrrhizic acid (GA) on diabetes-induced SMG damage. Experimental evaluation of GA treatment was conducted on a rat model of type I diabetes. Animals were assigned to three groups; control, diabetic and GA treated diabetic groups. After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. Also, parenchymal structures of the SMG were examined. GA alleviated the diabetes-induced SMG damage via restoring the SMG levels of oxidative stress markers and ET-1 almost near to the normal levels most probably via regulation of SIRT1, AQPs and accordingly LC-3, P62 and Beclin-1levels. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis.

scholarly journals The pathogen Moniliophthora perniciosa promotes differential proteomic modulation of cacao genotypes with contrasting resistance to witches´ broom disease.

2019 ◽  
Author(s):  
Everton Cruz Santos ◽  
Carlos Priminho Pirovani ◽  
Stephany Correa ◽  
Fabienne Micheli ◽  
Karina P Gramacho
Keyword(s):  
Oxidative Stress ◽  
Plant Pathogens ◽  
Durable Resistance ◽  
Trypsin Inhibitors ◽  
Post Inoculation ◽  
Biological Functions ◽  
Moniliophthora Perniciosa ◽  
Resistant Genotype ◽  
Broom Disease ◽  
Related Proteins

Abstract Background: Witches’ broom disease (WBD) of cacao (Theobroma cacao L.), caused by Moniliophthora perniciosa, is the most important limiting factor for the cacao production in Brazil. Hence, the development of cacao genotypes with durable resistance is the key challenge for control the disease. Proteomic methods are often used to study the interactions between hosts and pathogens, therefore helping classical plant breeding projects on the development of resistant genotypes. The present study compared the proteomic alterations between two cacao genotypes standard for WBD resistance and susceptibility, in response to M. perniciosa infection at 72 hours and 45 days post-inoculation; respectively the very early stages of the biotrophic and necrotrophic stages of the cacao x M. perniciosa interaction. Results: A total of 554 proteins were identified, being 246 in the susceptible Catongo and 308 in the resistant TSH1188 genotypes. The identified proteins were involved mainly in metabolism, energy, defense and oxidative stress. The resistant genotype showed more expressed proteins with more variability associated with stress and defense, while the susceptible genotype exhibited more repressed proteins. Among these proteins, stand out pathogenesis related proteins (PRs), oxidative stress regulation related proteins, and trypsin inhibitors. Interaction networks were predicted, and a complex protein-protein interaction was observed. Some proteins showed a high number of interactions, suggesting that those proteins may function as cross-talkers between these biological functions. Conclusions: We present the first study reporting the proteomic alterations of resistant and susceptible genotypes in the T. cacao x M. perniciosa pathosystem. The important altered proteins identified in the present study are related to key biologic functions in resistance, such as oxidative stress, especially in the resistant genotype TSH1188, that showed a strong mechanism of detoxification. Also, the positive regulation of defense and stress proteins were more evident in this genotype. Proteins with significant roles against fungal plant pathogens, such as chitinases, trypsin inhibitors and PR 5 were also identified, and they may be good resistance markers. Finally, important biological functions, such as stress and defense, photosynthesis, oxidative stress and carbohydrate metabolism were differentially impacted with M. perniciosa infection in each genotype.

Comparative whey proteome analysis of small-tailed Han and DairyMeade ovine milk

2021 ◽  
pp. 1-5
Author(s):  
Urhan Bai ◽  
Xiaohu Su ◽  
Zhong Zheng ◽  
Liguo Zhang ◽  
Ying Ma ◽  
...  
Keyword(s):  
Mammary Gland Development ◽  
Proteome Analysis ◽  
Dairy Sheep ◽  
Milk Traits ◽  
Beneficial Effects ◽  
Proteomic Approach ◽  
Tandem Mass Tag ◽  
Proteome Profile ◽  
Related Proteins ◽  
Gland Development

Abstract We characterized the proteome profile of mid-lactation small-tailed Han (STH) and DairyMeade (DM) ovine milk in order to explore physiological variation and differences in milk traits between the two breeds. Methodology combined a tandem mass tag (TMT) proteomic approach with LC-MS/MS technology. A total of 656 proteins were identified in STH and DM ovine milk, of which 17and 29 proteins were significantly upregulated (P < 0.05) in STH and DM, respectively. Immune-related proteins and disease-related proteins were highly expressed in STH milk, whereas S100A2 and AEBP1 were highly expressed in DM milk, which had beneficial effects on mammary gland development and milk yield. Our results provide a theoretical basis for future breeding of dairy sheep.

scholarly journals Insights into the Periplasmic Proteins of Acinetobacter baumannii AB5075 and the Impact of Imipenem Exposure: A Proteomic Approach

2019 ◽  
Vol 20 (14) ◽  
pp. 3451 ◽  
Author(s):  
Scribano ◽  
Marzano ◽  
Mortera ◽  
Sarshar ◽  
Vernocchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Protein Interactions ◽  
Biological Response ◽  
Bacterial Viability ◽  
Proteomic Approach ◽  
Periplasmic Proteins ◽  
General Response ◽  
The Impact

Carbapenem-resistant Acinetobacter baumannii strains cause life-threatening infections due to the lack of therapeutic options. Although the main mechanisms underlying antibiotic-resistance have been extensively studied, the general response to maintain bacterial viability under antibiotic exposure deserves to be fully investigated. Since the periplasmic space contains several proteins with crucial cellular functions, besides carbapenemases, we decided to study the periplasmic proteome of the multidrug-resistant (MDR) A. baumannii AB5075 strain, grown in the absence and presence of imipenem (IMP). Through the proteomic approach, 65 unique periplasmic proteins common in both growth conditions were identified: eight proteins involved in protein fate, response to oxidative stress, energy metabolism, antibiotic-resistance, were differentially expressed. Among them, ABUW_1746 and ABUW_2363 gene products presented the tetratricopeptide repeat motif, mediating protein-protein interactions. The expression switch of these proteins might determine specific protein interactions to better adapt to changing environmental conditions. ABUW_2868, encoding a heat shock protein likely involved in protection against oxidative stress, was upregulated in IMP-exposed bacteria. Accordingly, the addition of periplasmic proteins from A. baumannii cultured with IMP increased bacterial viability in an antioxidant activity assay. Overall, this study provides the first insights about the composition of the periplasmic proteins of a MDR A. baumannii strain, its biological response to IMP and suggests possible new targets to develop alternative antibiotic drugs.

scholarly journals DJ-1 Proteoforms in Breast Cancer Cells: The Escape of Metabolic Epigenetic Misregulation

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1968
Author(s):  
Domenica Scumaci ◽  
Erika Olivo ◽  
Claudia Vincenza Fiumara ◽  
Marina La Chimia ◽  
Maria Teresa De Angelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glycolytic Flux ◽  
Proliferative Potential ◽  
Moderate Increase ◽  
Reactive Carbonyl Species ◽  
Proteomic Approach ◽  
Age Related

Enhanced glycolysis is a hallmark of breast cancer. In cancer cells, the high glycolytic flux induces carbonyl stress, a damaging condition in which the increase of reactive carbonyl species makes DNA, proteins, and lipids more susceptible to glycation. Together with glucose, methylglyoxal (MGO), a byproduct of glycolysis, is considered the main glycating agent. MGO is highly diffusible, enters the nucleus, and can react with easily accessible lysine- and arginine-rich tails of histones. Glycation adducts on histones undergo oxidization and further rearrange to form stable species known as advanced glycation end-products (AGEs). This modification alters nucleosomes stability and chromatin architecture deconstructing the histone code. Formation of AGEs has been associated with cancer, diabetes, and several age-related diseases. Recently, DJ-1, a cancer-associated protein that protects cells from oxidative stress, has been described as a deglycase enzyme. Although its role in cell survival results still controversial, in several human tumors, its expression, localization, oxidation, and phosphorylation were found altered. This work aimed to explore the molecular mechanism that triggers the peculiar cellular compartmentalization and the specific post-translational modifications (PTM) that, occurring in breast cancer cells, influences the DJ-1 dual role. Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. Notably, this threonine is in addition to histidine 126, a key residue involved in the formation of catalytic triade (glu18-Cys106-His126) inside the glioxalase active site of DJ. Interestingly, we found that pharmacological modulation of Akt pathway induces a functional tuning of DJ-1 proteoforms, as well as their shuttle from cytosol to nucleus, pointing out that pathway as critical in the development of DJ-1 pro-tumorigenic abilities. Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation. In normal conditions, DJ-1 acts as a redox-sensitive chaperone and as an oxidative stress sensor. In cancer cells, glycolytic rewiring, inducing increased reactive oxygen species (ROS) levels, enhances AGEs products. Alongside, the moderate increase of ROS enhances Akt signaling that induces DJ-1-phosphorylation. When phosphorylated DJ-1 increases its glyoxalase activity, the level of AGEs on histones decreases. Therefore, phospho-DJ-1 prevents glycation-induced histones misregulation and its Akt-related hyperactivity represents a way to preserve the epigenome landscape sustaining proliferation of cancer cells. Together, these results shed light on an interesting mechanism that cancer cells might execute to escape the metabolic induced epigenetic misregulation that otherwise could impair their malignant proliferative potential.

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