Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling protein quantification in biofluids and tissues, thus taking toxicological research to the next level. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent studies regarding novel types of lysine acylation, their biological functions, and their applicationsin toxicoproteomics research.
Acetylation ; Acylation ; Aging ; Cell Cycle ; Lysine ; Protein Processing, Post-Translational ; Proteins ; Proteomics ; Toxicology

Although diaphragmatic eventration in newborn infants is generally regarded as a rare condition, the need for accurate diagnosis and appropriate intervention according to the etiological factors is well known. Recently authors experienced five consecutive cases of diaphragmatic eventration. All requiring surgery. All were seen within the second month of life ranging one to 55 days after birth. And all were male infants. All eventration were left sided. Respiratory symptoms were present in 4 cases, and the remainder had no symptoms other than inability to gain weight. The radiologic changes were pronounced in all cases, the dome of the diaphragm reaching from the third to fifth intercostal spaces. Regarding surgical technique, the authors favored Diaphragmatic plication through the abdomen, which gave excellent clinical and radiological results. No postoperative mortality was noted.
Abdomen ; Diagnosis ; Diaphragm ; Diaphragmatic Eventration* ; Humans ; Infant* ; Infant, Newborn ; Male ; Mortality ; Parturition

Mesenteric and omental cysts are rare lesions of childhood. These cysts are similar to cystic hygromas in other parts of the body morphologically and pathologically. From 1980 to 1997, 8 children were diagnosed and treated for mesenteric or omental cysts. Their ages ranged from 18 days to 6 years. There were 5 boys and 3 girls. The main presenting symptom was abdominal pain. Operative procedures were complete cysts excision, complete excision with intestinal resection, or complete excision with intestinal resection and colostomy. Accurate preoperative diagnosis was possible with the current ultrasonographic imaging techniques. Complete excision of the lesion was possible in all patients and resulted in an excellent outcome.
Abdominal Pain ; Child ; Colostomy ; Diagnosis ; Female ; Humans ; Lymphangioma, Cystic ; Mesenteric Cyst ; Surgical Procedures, Operative

Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms (IC50 values, 3.2-33.7 muM). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.
Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP2D6 ; Cytochrome P-450 CYP2E1 ; Cytochrome P-450 Enzyme System* ; Humans ; Hydrolysis ; Metabolism ; Microsomes, Liver ; Proadifen* ; Protein Isoforms

PURPOSE: We evaluated ocular optical components and their interrelationships in myopic Korean patients. METHODS: In this prospective observational study, 1,011 consecutive patients were recruited from a refractive surgery clinic. The best-corrected visual acuity was >20 / 20 in all patients. The refractive error, axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and vitreous chamber depth (VCD) were measured by an autorefractor and partial coherence laser interferometry (IOL Master). Central corneal thickness (CCT) was measured by ORBscan II topography. RESULTS: The refractive errors had a positive correlation with LT but negative correlations with AL, ACD, VCD, and CCT. As the axial length increased, the ACD, VCD, and CCT increased but the LT decreased. The CCT had a positive correlation with gender, refractive errors, ACD, VCD, and AL but no correlation with age. The mean CCT was increased in proportion to the increase in AL. CONCLUSIONS: In myopic Korean patients, as axial elongation progressed, the VCD and ACD deepened and the CCT thickened but the LT decreased. The CCT had a positive correlation with the degree of myopia and the AL.
Adult ; Female ; Humans ; Male ; Middle Aged ; Myopia/*epidemiology/therapy ; Prospective Studies ; Refractive Errors/*epidemiology/therapy ; Republic of Korea/epidemiology ; Visual Acuity

Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.
Alanine Transaminase ; Animals ; Antibody Formation ; Aspartate Aminotransferases ; Biotransformation ; Blotting, Western ; Corn Oil ; Cytochrome P-450 CYP2E1* ; Cytochrome P-450 Enzyme System ; Erythrocytes ; Female ; Humans ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Sheep ; Thioacetamide

Human malignant melanoma is an aggressive skin cancer which has been rising at a greater rate than any other cancers. Although various new therapeutic methods have been developed in previous studies, this disease has properties of high proliferation and metastasis rate which remain obstacles that have lead to a poor prognosis in patients. It has been reported that a specific Lactobacillus extract has anti-cancer and –metastasis effect in vitro and in vivo. However, previous research has not specified precisely what effect the Lactobacillus rhamnosus GG (LGG) extract has had on human malignant melanomas. In this study, we showed that the LGG extract has anti-cancer and –metastasis effects on the human malignant melanoma cell lines, A375P and A375SM. At first, it was found that, while the LGG extract affects human neonatal dermal fibroblasts slightly, it induced the dose-dependent anti-cancer effect on A375P and A375SM by a WST-1 proliferation assay. As a result of a real-time PCR analysis, the expression patterns of several genes related to cell cycle, proliferation, and apoptosis were modulating in a manner that inhibited the growth of both malignant melanoma cell lines after the treatment of the LGG extract. Furthermore, genes related to the epithelialmesenchymal transition were down-regulated, and migration rates were also decreased significantly by the LGG extract. Our study showed that the LGG extract could be used as a potential therapeutic source.
Apoptosis ; Cell Cycle ; Cell Line ; Epithelial-Mesenchymal Transition ; Fibroblasts ; Humans* ; In Vitro Techniques ; Lactobacillus rhamnosus* ; Lactobacillus* ; Melanoma* ; Neoplasm Metastasis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Skin Neoplasms

HSP90 is a molecular chaperone that increases the stability of client proteins. Cancer cells show higher HSP90 expression than normal cells because many client proteins play an important role in the growth and survival of cancer cells. HSP90 inhibitors mainly bind to the ATP binding site of HSP90 and inhibit HSP90 activity, and these inhibitors can be distinguished as ansamycin and non-ansamycin depending on the structure. In addition, the histone deacetylase inhibitors inhibit the activity of HSP90 through acetylation of HSP90. These HSP90 inhibitors have undergone or are undergoing clinical trials for the treatment of cancer. On the other hand, recent studies have reported that various reagents induce cleavage of HSP90, resulting in reduced HSP90 client proteins and growth suppression in cancer cells. Cleavage of HSP90 can be divided into enzymatic cleavage and non-enzymatic cleavage. Therefore, reagents inducing cleavage of HSP90 can be classified as another class of HSP90 inhibitors. We discuss that the cleavage of HSP90 can be another mechanism in the cancer treatment by HSP90 inhibition.
Acetylation ; Adenosine Triphosphate ; Binding Sites ; Drug Therapy ; Hand ; Heat-Shock Proteins ; Histone Deacetylase Inhibitors ; Hot Temperature ; Indicators and Reagents ; Molecular Chaperones ; Rifabutin

BACKGROUND AND OBJECTIVES: Embryonic stem (ES) cells have pluripotent ability to differentiate into multiple tissue lineages. SIRT1 is a class III histone deacetylase which modulates chromatin remodeling, gene silencing, cell survival, metabolism, and development. In this study, we examined the effects of SIRT1 inhibitors on the hematopoietic differentiation of mouse ES cells. METHODS AND RESULTS: Treatment with the SIRT1 inhibitors, nicotinamide and splitomicin, during the hematopoietic differentiation of ES cells enhanced the production of hematopoietic progenitors and slightly up-regulated erythroid and myeloid specific gene expression. Furthermore, treatment with splitomicin increased the percentage of erythroid and myeloid lineage cells. CONCLUSIONS: Application of the SIRT1 inhibitor splitomicin during ES cell differentiation to hematopoietic cells enhanced the yield of specific hematopoietic lineage cells from ES cells. This result suggests that SIRT1 is involved in the regulation of hematopoietic differentiation of specific lineages and that the modulation of the SIRT1 activity can be a strategy to enhance the efficiency of hematopoietic differentiation.
Animals ; Cell Differentiation ; Cell Survival ; Chromatin Assembly and Disassembly ; Gene Expression ; Gene Silencing ; Histone Deacetylases ; Metabolism ; Mice ; Mouse Embryonic Stem Cells ; Niacinamide

Background and Objectives: Embryonic stem (ES) cells have the capacity to self-renew and generate all types of cells.MUC1-C, a cytoplasmic subunit of MUC1, is overexpressed in various carcinomas and mediates signaling pathways to regulate intracellular metabolic processes and gene expression involved in the maintenance of cancer cells. However, the functional role of MUC1-C in ES cells is not well understood. In this study, we investigated the role of MUC1-C on growth, survival,: and differentiation of mouse ES (mES) cells. Methods: and Results: Undifferentiated mES cells expressed the MUC1-C protein and the expression level was decreased during differentiation. Inhibition of MUC1-C, by the specific inhibitor GO201, reduced proliferation of mES cells.However, there was no prominent effect on pluripotent markers such as Oct4 expression and STAT3 signaling, and MUC1-C inhibition did not induce differentiation. Inhibition of MUC1-C increased the G1 phase population, decreased the S phase population, and increased cell death. Furthermore, inhibition of MUC1-C induced disruption of the ROS balance in mES cells. Conclusions These results suggest that MUC1-C is involved in the growth and survival of mES cells.