KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

基礎講座 電気泳動(Electrophoresis)

The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

Biochemistry of oxidative stress

// Berthony Deslouches 1, 2 and Y. Peter Di 1 1 Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA 2 Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Correspondence to: Berthony Deslouches, email: tdesl19@pitt.edu Y. Peter Di, email: peterdi@pitt.edu Keywords: antimicrobial peptides, anticancer peptides, host defense peptides, antitumor peptides, cationic peptides Received: December 16, 2016      Accepted: March 20, 2017      Published: March 31, 2017 ABSTRACT In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

/pdf/antimicrobial-peptides-with-selective-antitumor-mechanisms-37gudob4vm.pdf

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.

Zinc alpha 2-glycoprotein (ZAG) is a protein of interest because of its ability to play many important functions in the human body, including fertilization and lipid mobilization After the discovery of this molecule, during the last 5 decades, various studies have been documented on its structure and functions, but still, it is considered as a protein with an unknown function Its expression is regulated by glucocorticoids Due to its high sequence homology with lipid-mobilizing factor and high expression in cancer cachexia, it is considered as a novel adipokine On the other hand, structural organization and fold is similar to MHC class I antigen-presenting molecule; hence, ZAG may have a role in the expression of the immune response The function of ZAG under physiologic and cancerous conditions remains mysterious but is considered as a tumor biomarker for various carcinomas There are several unrelated functions that are attributed to ZAG, such as RNase activity, regulation of melanin production, hindering tumor proliferation, and transport of nephritic by-products This article deals with the discussion of the major aspects of ZAG from its gene structure to function and metabolism

https://mcr.aacrjournals.org/content/molcanres/6/6/892.full.pdf

Zinc alpha 2-glycoprotein: a multidisciplinary protein.

The expression of high-abundance serum proteins in newly diagnosed patients with endometrial adenocarcinoma (EACa), squamous cell cervical carcinoma (SCCa) and cervical adenocarcinoma (ACCa), relative to control female subjects, was analyzed by subjecting serum samples to 2-DE followed by image analysis of the silver-stained protein profiles. The three cohorts of cancer patients demonstrated different altered expression of serum high-abundance proteins compared to negative control women. The expression of alpha1-antitrypsin, alpha1-B glycoprotein, cleaved high-molecular-weight kininogen (light chain) and antithrombin III were consistently altered in all the patients. However, clusterin was upregulated only in the patients with EACa, while those with SCCa and ACCa were typically characterized by the upregulated expression of zinc alpha-2-glycoprotein. The aberrant expression of selective serum proteins in the various cohorts of cancer patients was validated by competitive ELISA as well as by lectin detection. Analysis by using the champedak galactose binding lectin further highlighted an unidentified protein that may be differently glycosylated in the sera of the EACa patients that were studied.

/pdf/expression-of-high-abundance-proteins-in-sera-of-patients-1qxac1ubfq.pdf

Expression of high‐abundance proteins in sera of patients with endometrial and cervical cancers: Analysis using 2‐DE with silver staining and lectin detection methods

A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-α-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.

Lectin-based electrophoretic analysis of the expression of the 35 kDa inter-α-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignancies

The association between the acute-phase reactant proteins (APRPs) and cancer has long been established. There have been numerous reports correlating altered levels of various APRPs with different types of cancers. However, researchers are often quick to dismiss the use of these APRPs as potential biomarkers for the diagnosis and monitoring of cancer because alterations in APRP concentrations are observed in a wide range of diseases. Recent progress in proteomics studies which profiled the serum proteins of cancer patients and those of normal individuals indicated that the altered APRP expressions were different for distinct types, subtypes, and even stages of cancer. Interestingly, these data are in agreement with those observed earlier using immunochemical and biochemical assays. In view of this compelling association of different patterns of APRPs with various types of cancers and in an apparent shift of paradigm, we present in this review some indications that APRP fingerprinting may be used as complementary cancer biomarkers.

/pdf/can-the-acute-phase-reactant-proteins-be-used-as-cancer-1c7sfouv2h.pdf

Can the acute-phase reactant proteins be used as cancer biomarkers?

Background 
Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach.
Methodology and Principal Findings 
The whole cell proteome profiles of CHIKV-infected and mock control WRL-68 cells were compared and analyzed using two-dimensional gel electrophoresis (2-DGE). Fifty-three spots were found to be differentially modulated and 50 were successfully identified by MALDI-TOF/TOF. Eight were significantly up-regulated and 42 were down-regulated. The mRNA expressions of 15 genes were also found to correlate with the corresponding protein expression. STRING network analysis identified several biological processes to be affected, including mRNA processing, translation, energy production and cellular metabolism, ubiquitin-proteasome pathway (UPP) and cell cycle regulation.
Conclusion/Significance 
This study constitutes a first attempt to investigate alteration of the host cellular proteome during early CHIKV infection. Our proteomics data showed that during early infection, CHIKV affected the expression of proteins that are involved in mRNA processing, host metabolic machinery, UPP, and cyclin-dependent kinase 1 (CDK1) regulation (in favour of virus survival, replication and transmission). While results from this study complement the proteomics results obtained from previous late host response studies, functional characterization of these proteins is warranted to reinforce our understanding of their roles during early CHIKV infection in humans.

/pdf/differential-proteome-analysis-of-chikungunya-virus-339b4p21lz.pdf

Differential Proteome Analysis of Chikungunya Virus Infection on Host Cells

Background
Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples.

/pdf/profiling-of-serum-and-tissue-high-abundance-acute-phase-8xf0en42fr.pdf

Puteri Shafinaz Abdul-Rahman

Papers

Expression of high‐abundance proteins in sera of patients with endometrial and cervical cancers: Analysis using 2‐DE with silver staining and lectin detection methods

Lectin-based electrophoretic analysis of the expression of the 35 kDa inter-α-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignancies

Can the acute-phase reactant proteins be used as cancer biomarkers?

Differential Proteome Analysis of Chikungunya Virus Infection on Host Cells

Profiling of serum and tissue high abundance acute-phase proteins of patients with epithelial and germ line ovarian carcinoma.