scholarly journals Proteomic analysis of decidua in patients with recurrent pregnancy loss (RPL) reveals mitochondrial oxidative stress dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiang-Jie Yin ◽  
Wei Hong ◽  
Fu-Ju Tian ◽  
Xiao-Cui Li

Abstract Background Pregnancy is a complicated physiological process. The multifaceted regulation of maternal–fetal interface is of great importance for maintaining normal pregnancy and avoiding fetal rejection and secondary abortion. Previous studies have focused on the clinical features or pathological biomarkers of fetal rejection and abortion. However, no significant breakthrough has been made. Therefore, it is important to understand the molecular mechanisms of recurrent pregnancy loss (RPL) to identify potential therapeutic strategies. The aim of this study was to investigate the pathogenesis of RPL. Methods In this study, Relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was used to identify differentially expressed proteins in decidual from RPL patients and matched normal controls. Further, Molecules NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 (ndufb3) and cyclooxygenase-2 (COX-2) were validated by immunohistochemistry (IHC), Western blotting, CCK8 and mitochondrial red fluorescent probe (Mito-Tracker Red CMXRos). Results A total of 456 proteins reached the threshold of a 1.5-fold change were identified for further bioinformatics analysis. Upon mapping the differentially expressed proteins using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways database, iTRAQ results were confirmed by assessing NDUFB3 and COX-2 protein levels in specimens of decidual tissue by Western blotting. Our study indicates that the level of COX-2 and NDUFB3 were significantly increased in decidual cell from RPL patients. Overexpression of NDUFB3 inhibited cell vitality and oxidative stress of decimal cell. Further, our found that overexpression NDUFBD3 in decidual cell decreased the mitochondrial membrane potential expression levels. These results suggest that NDUFB3 might play an important role in promote the pathological process of RPL. Conclusions This comprehensive analysis of RPL proteomics reveals novel candidate: NDUFB3, which could be further investigated for explanation of the pathological mechanism of RPL.

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Suxiang Lu ◽  
Qian Xiong ◽  
Kang Du ◽  
Xiaoni Gan ◽  
Xuzhen Wang ◽  
...  

Abstract Background Polypterus senegalus can fully regenerate its pectoral lobed fins, including a complex endoskeleton, with remarkable precision. However, despite the enormous potential of this species for use in medical research, its regeneration mechanisms remain largely unknown. Methods To identify the differentially expressed proteins (DEPs) during the early stages of lobed fin regeneration in P. senegalus, we performed a differential proteomic analysis using isobaric tag for relative and absolute quantitation (iTRAQ) approach based quantitative proteome from the pectoral lobed fins at 3 time points. Furthermore, we validated the changes in protein expression with multiple-reaction monitoring (MRM) analysis. Results The experiment yielded a total of 3177 proteins and 15,091 unique peptides including 1006 non-redundant (nr) DEPs. Of these, 592 were upregulated while 349 were downregulated after lobed fin amputation when compared to the original tissue. Bioinformatics analyses showed that the DEPs were mainly associated with Ribosome and RNA transport, metabolic, ECM-receptor interaction, Golgi and endoplasmic reticulum, DNA replication, and Regulation of actin cytoskeleton. Conclusions To our knowledge, this is the first proteomic research to investigate alterations in protein levels and affected pathways in bichirs’ lobe-fin/limb regeneration. In addition, our study demonstrated a highly dynamic regulation during lobed fin regeneration in P. senegalus. These results not only provide a comprehensive dataset on differentially expressed proteins during the early stages of lobe-fin/limb regeneration but also advance our understanding of the molecular mechanisms underlying lobe-fin/limb regeneration.


2021 ◽  
Vol 14 ◽  
Author(s):  
Changci Tong ◽  
Peifang Cong ◽  
Ying Liu ◽  
Xiuyun Shi ◽  
Lin Shi ◽  
...  

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.


2019 ◽  
Vol 16 (4) ◽  
pp. 314-329
Author(s):  
Asma Babar ◽  
Tserang Donko Mipam ◽  
Shixin Wu ◽  
Chuanfei Xu ◽  
Mujahid Ali Shah ◽  
...  

<P>Background: Yaks inhabit high-altitude are well-adapted to the hypoxic environments. Though, the mechanisms involved in regulatory myocardial protein expression at high-altitude were not completely understood. </P><P> Objective: To revel the molecular mechanism of hypoxic adaptation in yak, here we have applied comparative myocardial proteomics in between yak and cattle by isobaric Tag for Relative and Absolute Quantitation (iTRAQ) labelling. </P><P> Methods: To understand the systematic protein expression variations in myocardial tissues that explain the hypoxic adaptation in yak, we have performed iTRAQ analysis combined with Liquid Chromatography- Tandem Mass Spectrometry (LC-MS/MS). Bioinformatics analysis was performed to find the association of these Differentially Expressed Proteins (DEPs) in different functions and pathways. Protein to protein interaction was analyzed by using STRING database. </P><P> Results: 686 Differentially Expressed Proteins (DEPs) were identified in yak with respect to cattle. From which, 480 DEPs were up-regulated and 206 were down-regulated in yak. Upregulated expression of ASB4, STAT, HRG, RHO and TSP4 in yak may be associated with angiogenesis, cardiovascular development, response to pressure overload to heart and regulation of myocardial contraction in response to increased oxygen tension. The up-regulation of mitochondrial proteins, ACAD8, GPDH-M, PTPMT1, and ALDH2, may have contributed to oxidation within mitochondria, hypoxia-induced cell metabolism and protection of heart against cardiac ischemic injuries. Further, the upregulated expression of SAA1, PTX, HP and MBL2 involved in immune response potentially helpful in myocardial protection against ischemic injuries, extracellular matrix remodeling and free heme neutralization/ clearance in oxygen-deficient environment. </P><P> Conclusion: Therefore, the identification of these myocardial proteins in will be conducive to investigation of the molecular mechanisms involved in hypoxic adaptations of yaks at high-altitude condition.</P>


2019 ◽  
Vol 16 (4) ◽  
pp. 297-306
Author(s):  
Chunhua Luo ◽  
Defu Yao ◽  
Teck Kwang Lim ◽  
Qingsong Lin ◽  
Yingfu Liu

Background:The molecular mechanisms or valuable biomarkers for early diagnosis of colorectal cancer (CRC) are not fully elucidated yet.Objective:To understand the proteomic changes at the global level in the carcinogenesis of CRC, differentially expressed proteins between normal intestinal epithelial cells CCD841 and colorectal cancer cells HCT116 were identified.Method:The isobaric tags for relative and absolute quantitation (iTRAQ) coupled with 2D LC-MS/MS proteomic approach were performed for screening the altered proteins between cells CCD841 and HCT116.Results:A total of 1947 proteins were identified after filtering and using a 1% false discovery rate. Based on a final cutoff (> 3.16 and < 0.32), 229 proteins were found to be significantly altered, among which 95 (41%) were up-regulated while 134 (59%) were down-regulated. Gene Ontology analysis revealed that the differentially expressed proteins were mainly cell part proteins involved in cellular process and binding in terms of subcellular distribution, biological process, and molecular function. KEGG analysis indicated that the differentially expressed proteins were significantly involved in the process of focal adhesion, pathogenic Escherichia coli infection, leukocyte transendothelial migration, bacterial invasion of epithelial cells, regulation of actin cytoskeleton, DNA replication and so on.Conclusion:Collectively, our data identified differentially expressed proteins in colon cancer carcinogenesis, which could provide the clues on unraveling the molecular mechanism of CRC.


Gene ◽  
2021 ◽  
Vol 768 ◽  
pp. 145334
Author(s):  
Deeba S. Jairajpuri ◽  
Zainab H. Malalla ◽  
Naeema Mahmood ◽  
Farah Khan ◽  
Wassim Y. Almawi

2019 ◽  
Vol 133 ◽  
pp. 18-26 ◽  
Author(s):  
Ramyar Azizi ◽  
Mohammad Sadegh Soltani-Zangbar ◽  
Golshan sheikhansari ◽  
Zahra Pourmoghadam ◽  
Amir Mehdizadeh ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. 76
Author(s):  
Jian-Yu Meng ◽  
Mbuya Sylvain Ntambo ◽  
Philippe C. Rott ◽  
Hua-Ying Fu ◽  
Mei-Ting Huang ◽  
...  

Sugarcane can suffer severe yield losses when affected by leaf scald, a disease caused by Xanthomonas albilineans. This bacterial pathogen colonizes the vascular system of sugarcane, which can result in reduced plant growth and plant death. In order to better understand the molecular mechanisms involved in the resistance of sugarcane to leaf scald, a comparative proteomic study was performed with two sugarcane cultivars inoculated with X. albilineans: one resistant (LCP 85-384) and one susceptible (ROC20) to leaf scald. The iTRAQ (isobaric tags for relative and absolute quantification) approach at 0 and 48 h post-inoculation (hpi) was used to identify and annotate differentially expressed proteins (DEPs). A total of 4295 proteins were associated with 1099 gene ontology (GO) terms by GO analysis. Among those, 285 were DEPs during X. albilineans infection in cultivars LCP 85-384 and ROC20. One hundred seventy-two DEPs were identified in resistant cultivar LCP 85-384, and 113 of these proteins were upregulated and 59 were downregulated. One hundred ninety-two DEPs were found in susceptible cultivar ROC20 and half of these (92) were upregulated, whereas the other half corresponded to downregulated proteins. The significantly upregulated DEPs in LCP 85-384 were involved in metabolic pathways, the biosynthesis of secondary metabolites, and the phenylpropanoid biosynthesis pathway. Additionally, the expression of seven candidate genes related to photosynthesis and glycolytic pathways, plant innate immune system, glycosylation process, plant cytochrome P450, and non-specific lipid transfer protein was verified based on transcription levels in sugarcane during infection by X. albilineans. Our findings shed new light on the differential expression of proteins in sugarcane cultivars in response to infection by X. albilineans. The identification of these genes provides important information for sugarcane variety improvement programs using molecular breeding strategies.


Oncotarget ◽  
2018 ◽  
Vol 9 (99) ◽  
pp. 37344-37344
Author(s):  
Lindsay F. Goodale ◽  
Soren Hayrabedyan ◽  
Krassimira Todorova ◽  
Roumen Roussev ◽  
Sivakumar Ramu ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Huai-Dong Hu ◽  
Feng Ye ◽  
Da-Zhi Zhang ◽  
Peng Hu ◽  
Hong Ren ◽  
...  

Multidrug resistance (MDR) is a major obstacle towards a successful treatment of gastric cancer. However, the mechanisms of MDR are intricate and have not been fully understood. To elucidate the molecular mechanisms of MDR in gastric cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the vincristine-resistant SGC7901/VCR cell line and its parental SGC7901 cell line as a model. In total, 820 unique proteins were identified and 91 proteins showed to be differentially expressed in SGC7901/VCR compared with SGC7901. Several differentially expressed proteins were further validated by western blot analysis. Furthermore, the association of MVP, one of the highly expressed proteins in SGC7901/VCR, with MDR was verified. Our study is the first application of iTRAQ technology for MDR mechanisms analysis in gastric cancer, and many of the differentially expressed proteins identified have not been linked to MDR in gastric cancer before, which showed the value of this technology in identifying differentially expressed proteins in cancer.


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