• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.12
• /
• pp.4803-4812
• /
• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• Molecules and Cells
• /
• v.39 no.3
• /
• pp.186-194
• /
• 2016

Epidemiological evidence suggests that bone is especially sensitive to oxidative stress, causing bone loss in the elderly. Previous studies indicated that human amnion-derived mesenchymal stem cells (HAMSCs), obtained from human amniotic membranes, exerted osteoprotective effects in vivo. However, the potential of HAMSCs as seed cells against oxidative stress-mediated dysfunction is unknown. In this study, we systemically investigated their antioxidative and osteogenic effects in vitro. Here, we demonstrated that HAMSCs significantly promoted the proliferation and osteoblastic differentiation of $H_2O_2$-induced human bone marrow mesenchymal stem cells (HBMSCs), and down-regulated the reactive oxygen species (ROS) level. Further, our results suggest that activation of the ERK1/2 MAPK signal transduction pathway is essential for both HAMSCs-mediated osteogenic and protective effects against oxidative stress-induced dysfunction in HBMSCs. U0126, a highly selective inhibitor of extracellular ERK1/2 MAPK signaling, significantly suppressed the antioxidative and osteogenic effects in HAMSCs. In conclusion, by modulating HBMSCs, HAMSCs show a strong potential in treating oxidative stress- mediated bone deficiency.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.3
• /
• pp.327-334
• /
• 2017

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established $Ca^{2+}$ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular $Ca^{2+}$ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular $Ca^{2+}$ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than $10{\mu}m$, induced intracellular $Ca^{2+}$ signaling, which was mediated by extracellular $Ca^{2+}$. The PM10-mediated intracellular $Ca^{2+}$ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

• Journal of Korean Ophthalmic Optics Society
• /
• v.13 no.3
• /
• pp.103-109
• /
• 2008

Purpose: This review illustrates an importance of oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation in association with eye disease, especially of cataract, and discusses an important role of lipid peroxide as a mediator of oxidative stress-related ocular dysfunction. Methods: Oxidative stress, resulted from the cellular production of ROS and RNS, is known to cause various forms of cellular damages such as protein oxidation, DNA breaks, apoptosis, and lipid peroxidation. These damages can be developed to human diseases. Accumulating evidence strongly suggests that continuous or constant exposure of eye tissues to oxidative stress is a main cause of cataractogenesis. Therefore, we investigated the action of oxidative stress in ocular dysfunction. Results: The ocular lens is continuously attacked by ROS inevitable generated from the process of cellular metabolism and the chronic exposure to ultraviolet. Excessive generation of ROS, resulting in degradation, oxidation, crosslinking and aggregation of lens proteins, is regarded as an important factor in development of cataract. Conclusions: These oxidative stress and oxidant/antioxidant imbalance produces the excess ROS which can lead to eye dysfunction. Even though known results, it should be noted that there is limited information on the molecular mechanism which can be better defined with the interrelation of oxidative stress and optic abnormalities.

• Environmental Analysis Health and Toxicology
• /
• v.21 no.1 s.52
• /
• pp.71-79
• /
• 2006

Epidemiologic studies have showed a close correlation between arsenic exposure and heart disease such as, cardiovascular problem, ischemic heart disease, infarction, atherosclerosis and hypertension in human. It may increase the mortality of high risk group with heart disease. Regarding the mechanism studies of heart failure, blood vessel, vascular smooth muscle cells and endothelial cells have long been focused as the primary targets in arsenic exposure but there are only a few studies on the cardiomyocytes. In this study, the generation of oxidative stress by low dose of arsenic trioxide was investigated in rat cardiomyocytes. By direct measurement of reactive oxygen species and fluorescent microscopic observation using fluorescent dye 2',7'-dichlorofluorescin diacetate, reactive oxygen species were found to be generated without cell death, where cells are treated with 0.1 ppm arsenic for 24 hours. With the induction of reactive oxygen species, GSH level was decreased by the same treatment. However, DNA damage did not seem to be serious by DAPI staining, while high dose of arsenic (2 ppm for 24 hrs) caused fragmentation of DNA. To identify the molecular biomarkers of low-dose arsenic exposure, gene expression was also investigated with whole genome microarray. As results, 9,022 genes were up-regulated including heme oxygenase-l and glutathione S-transrerase, which are well-known biomarkers of oxidative stress. 9,404 genes were down-regulated including endothelial type gp 91-phox gene by the treatment of 0.1 ppm arsenic for 24 hours. This means that biological responses of cardiomyocytes may be altered by ROS induced by low level arsenic without cell death, and this alteration may be detected clearly by molecular biomarkers such as heme oxygenase-1.

• Journal of Environmental Health Sciences
• /
• v.30 no.3
• /
• pp.230-238
• /
• 2004

The adverse health effects of a number of environment pollutions are related to the formation of free radicals. Induction of antioxidant defensive system in the response to an oxidative attack is an essential element of the cell to survive. CYP2E1 is easily induced by organic solvents and induces continuous formation of reactive oxygen species (ROS). ${\gamma}$-Glutamyltranspeptidase (${\gamma}$GT) plays an important role in glutathione metabolism and xenobiotic detoxification. To evaluate the characteristic of oxidative stress which induces GGT expression and to understand human antioxidant defensive response against oxidative stress induced by CYP2E1, we studied regulation of ${\gamma}$GT enzyme expression in response to various oxidative stresses in human HepG2 cells. The ${\gamma}$GT activity was not modified after exposure of acute oxidative stress inducing agents (ferric nitrilotriacetate, cumene hydroperoxide, ADP-Fe, O-tetradecanoylphorbol-13-acetate, tumor necrosis factor-alpha). To induce continuous exposure of cells to ROS, HepG2 cells were transfected by human CYP2E1 gene transiently. The CYP2E1 activity was verified with chlorzoxazone hydroxylation. Transfection of CYP2E1 showed continuous 60% increase in intracellular ROS and 240 % increase in microsomal ROS. CYP2E1 overexpressing cells showed increased ${\gamma}$GT activity (2.5-fold). The observed enhancement of ${\gamma}$GT activity correlated with a significant increase of ${\gamma}$GT mRNA (2.1-fold). Treatment with antioxidant strongly prevented the increase in ${\gamma}$GT activity. The CYP2E1 overexpression did not modify toxicity index and increased glutathione levels. These results show that continuous exposure of cells to ROS produced by CYP2E1 up-regulates ${\gamma}$GT; This may be one of the adaptive antioxidant responses of cells to oxidative insult. Present study also suggests that the induction of ${\gamma}$GT could be used as a marker of oxidative stress induced by exposure to organic solvents.

• 대한생식의학회:학술대회논문집
• /
• 2000.06a
• /
• pp.29-35
• /
• 2000

The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had Idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean ${\pm}$ SE, 3.25 ${\pm}$ 0.89) and vasectomy reversals (2.65 ${\pm}$ 1.01). All infertility groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 ${\pm}$ 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 ${\pm}$ 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and Is superior to ROS or TAC alone in discriminating between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.

• Korean journal of food and cookery science
• /
• v.28 no.6
• /
• pp.821-828
• /
• 2012

In an attempt to identify the neuroprotective effect of Cudrania tricuspidata (CT) leaves against ROS (reactive oxygen species)-induced oxidative stress in neuronal cells, the extracts from CT leaves were investigated using PC12 cells and N18-RE-105 cells. The methanolic and ethanolic extracts from CT were denoted as CTM (Cudrania tricuspidata Leaves methanolic extracts) and CTE (Cudrania tricuspidata Leaves ethanolic extracts), respectively. The neuroprotective effects of the extracts were measured by DCF-DA assay, MTT reduction assay, and LDH release assay. The PC12 cells exposed to $H_2O_2$-induced oxidative stress and the N18-RE-105 cells exposed to glutamate-induced oxidative stress were treated with various concentrations of CTM and CTE. The results, CTM treatments resulted in the induction of a dose-dependent protective effect in PC12 cells and N18-RE-105 cells. Interestingly, CTE also showed neuroprotective effect in PC12 cells and N18-RE-105 cells. Therefore, these results suggest that CTM and CTE could be a new potential candidate as neuroprotective agents against ROS-induced oxidative stress in neuronal cells.

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.68-74
• /
• 2012

Anthocyanins have received growing attention as dietary antioxidants for the prevention of oxidative damage. Astrocytes, which are specialized glial cells, exert numerous essential, complex functions in both healthy and diseased central nervous system (CNS) through a process known as reactive astrogilosis. Therefore, the maintenance of glial cell viability may be important because of its role as a key modulator of neuropathological events. The aim of this study was to investigate the effect of anthocyanin on the survival of glial cells exposed to oxidative stress. Our results demonstrated that anthocyanin extracts from black soybean increased survival of U87 glioma cells in a dose dependent manner upon oxygen-glucose deprivation (OGD), accompanied by decrease levels of reactive oxygen species (ROS). While treatment cells with anthocyanin extracts or OGD stress individually activated autophagy induction, the effect was signifi cantly augmented by pretreatment cells with anthocyanin extracts prior to OGD. The contribution of autophagy induction to the protective effects of anthocyanin was verifi ed by the observation that silencing the Atg5 expression, an essential regulator of autophagy induction, reversed the cytoprotective effect of anthocyanin extracts against OGD stress. Treatment of U87 cells with rapamycin, an autophagy inducer, increased cell survival upon OGD stress comparable to anthocyanin, indicating that autophagy functions as a survival mechanism against oxidative stress-induced cytotoxicity in glial cells. Our results, therefore, provide a rationale for the use of anthocyanin as a preventive agent for brain dysfunction caused by oxidative damage, such as a stroke.

• Environmental Analysis Health and Toxicology
• /
• v.18 no.3
• /
• pp.165-174
• /
• 2003

Cr (Ⅵ) - containing compounds are well-established carcinogens, although the mechanism for chromium - induced carcinogenesis is still not well understood. The reduction of Cr (Ⅵ) to its lower oxidation states, par ticularly Cr (V) and Cr (IV), is an important step for the production of chromium-mediated reactive oxygen species (ROS). The persistent oxidative stress during the reduction process may play a key role in the mechanism of Cr (Ⅵ) -induced carcinogenesis. This paper summarizes recent studies on (1) the reduction of Cr (Ⅵ) to Cr (III) occur by a multiplicity of mechanisms depending on the nature of reducing agents including ascorbate, diol-and thiol-containing molecules, certain flavoenzymes, cell organelles, intact cells, and whole animals; (2) free-radical production with emphasis on hydroxy radical generation via Fenton or Haber-Weiss type reactions; and (3) free radical - induced cellular damage, such at DNA strand breaks, hydroxylation of 2'-deoxyguanosine, and activation of nuclear transcription factor kB.