Biomedical subjects

Xianglin Shi

Publications and source records attributed to Xianglin Shi.

At least 19 recordsLinked to original sources

PubMed2006

Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation.

Pyrin domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity against intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors, known as PYD-Nod-like receptors (NLR), PAN, PYPAF, NALP, Nod, and Caterpiller proteins, to the activation of downstream effectors, including activation of caspase-1 and NF-kappaB. Activation of these effectors occurs when specific protein complexes, known as inflammasomes, are formed. PYD signal transduction leads to inflammasome assembly and activation of specific effector proteins. It is modulated by a cellular PYD-only protein (cPOP1), which binds to ASC and interferes with the recruitment of ASC to activated PYD-NLRs. Here we describe the identification and characterization of a second cellular POP (cPOP2), which shows highest homology to the PYD of PAN1. cPOP2 binds to ASC and PAN1, thereby blocking formation of cryopyrin and PAN1-containing inflammasomes, activation of caspase-1, and subsequent processing and secretion of bioactive interleukin-1beta. Existence of a second cPOP provides additional insights into inflammasome formation and suggests that POPs might be a common regulatory mechanism to "fine-tune" the activity of specific PYD-NLR family protein-containing inflammasomes.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Identification of a critical site in Wld(s): essential for Nmnat enzyme activity and axon-protective function.

The chimeric Wld(s) protein consisting of the N-terminal 70 amino acids of Ufd2 and the complete sequence of nicotinamide mononucleotide adenylyltransferase1 (Nmnat1), delays Wallerian degeneration in Wld(s) mice. Although Nmnat1 enzyme activity was showed to be critical for the function of Wld(s) protein, the expected phenotype was not observed in Nmnat1 transgenic mice. To further check whether Nmnat1 enzyme activity is involved, we aligned sequences of eukaryotic Nmnats, and found that Phe in helix A is highly conserved not only in various species, but also in different homologues. The Phe is a residue located near to the highly conserved GXFXPX(T/H)XXH motif and resides in the same helix as the last His of this conserved motif. To investigate the role of the conserved Phe in Nmnat activity, we made the point mutation of Phe. The Phe28 mutation of mouse Nmnat1 in Wld(s) completely abolished its Nmnat enzyme activity. To study the role of mutant Wld(s) in axon degeneration, herpes viruses were packaged to infect cultured SCGs. We found that the mutant Wld(s) failed to protect axon degeneration from morphological changes, microtubule integration and neurofilament degradation. Therefore, we have identified a Phe residue that critical for both enzyme activity of Nmnat and the axon-protective function of Wld(s), and further confirmed that Nmnat1 enzyme activity is required in Wld(s) function.

Animals↗

PubMed2006

Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression.

Apigenin is a non-toxic dietary flavonoid with anti-tumor properties. We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition. However, the effect of apigenin in angiogenesis remains to be elucidated. Angiogenesis is the formation of new blood vessels and is required for tumor growth and metastasis. In this study, we showed that apigenin-inhibited expression of HIF-1 and VEGF in different cancer cells under both normoxic and hypoxic conditions. We demonstrated that apigenin significantly inhibited tumor angiogenesis in vivo, by using both the chicken chorioallantoic membrane and Matrigel plug assays. The inhibition of tumor angiogenesis was associated with the decrease of HIF-1 and VEGF in tumor tissues. Taken together, our results show that apigenin suppresses tumor angiogenesis through HIF-1 and VEGF expression.

Animals↗

PubMed2006

Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1alpha expression through activation of AKT and P70S6K1 in human ovarian cancer cells.

The epidermal growth factor (EGF) and EGF receptor (EGFR) family are often overexpressed in various human cancers including ovarian cancer. While it is generally believed that reactive oxygen species (ROS) are involved in the intracellular signaling events, the role of ROS in EGF-induced angiogenesis and carcinogenesis remains to be elucidated. The present study investigated the role of ROS in the regulation of AKT, p70S6K1, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1 (HIF-1) in ovarian cancer cells. In this study, OVCAR-3 cells were treated with EGF and catalase, an H2O2 scavenger. EGF treatment increases H2O2 production, leading to activation of the AKT/p70S6K1 pathway, resulting in increased VEGF expression at the transcriptional level. The inhibition of H(2)O(2) production by catalase abolished EGF-induced AKT and p70S6K1 activation, and VEGF expression through HIF-1alpha expression. Forced expression of p70S6K1 and HIF-1alpha reversed catalase- and rapamycin-inhibited VEGF transcriptional activation. We also showed that rapamycin, p70S6K1 inhibitor and catalase overexpression inhibited tumor angiogenesis. This study demonstrates a novel mechanism of EGF-induced VEGF and HIF-1alpha expression through production of H2O2 and activation of AKT and p70S6K1 in human ovarian cancer cells. This study also indicates that p70S6K1 and H2O2 are important in tumor angiogenesis. The results of the study could have an important implication in ovarian cancer therapy.

Animals↗

PubMed2006

Predicting cancer drug response by proteomic profiling.

PURPOSE: Accurate prediction of an individual patient's drug response is an important prerequisite of personalized medicine. Recent pharmacogenomics research in chemosensitivity prediction has studied the gene-drug correlation based on transcriptional profiling. However, proteomic profiling will more directly solve the current functional and pharmacologic problems. We sought to determine whether proteomic signatures of untreated cells were sufficient for the prediction of drug response. EXPERIMENTAL DESIGN: In this study, a machine learning model system was developed to classify cell line chemosensitivity exclusively based on proteomic profiling. Using reverse-phase protein lysate microarrays, protein expression levels were measured by 52 antibodies in a panel of 60 human cancer cell (NCI-60) lines. The model system combined several well-known algorithms, including random forests, Relief, and the nearest neighbor methods, to construct the protein expression--based chemosensitivity classifiers. The classifiers were designed to be independent of the tissue origin of the cells. RESULTS: A total of 118 classifiers of the complete range of drug responses (sensitive, intermediate, and resistant) were generated for the evaluated anticancer drugs, one for each agent. The accuracy of chemosensitivity prediction of all the evaluated 118 agents was significantly higher (P < 0.02) than that of random prediction. Furthermore, our study found that the proteomic determinants for chemosensitivity of 5-fluorouracil were also potential diagnostic markers of colon cancer. CONCLUSIONS: The results showed that it was feasible to accurately predict chemosensitivity by proteomic approaches. This study provides a basis for the prediction of drug response based on protein markers in the untreated tumors.

Antineoplastic Agents↗

PubMed2006

MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2.

Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. We have previously demonstrated that over-expression of ErbB2 promoted ethanol-mediated invasion of mammary epithelial cells and breast cancer cells. However, the underlying cellular/molecular mechanisms remain unknown. By gelatin zymography, we showed that over-expression of ErbB2 increased the production of matrix metalloproteinase-2 (MMP-2) and MMP-9 in human mammary epithelial cells (HB2). Transient or stable transfection of ErbB2 cDNA to HB2 cells upregulated the transcripts and the activity of the MMP-2/-9 gene promoter; the upregulation of MMP-2/-9 expression was mediated by p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (PI3K). Although ethanol, at physiologically relevant concentrations (100-400 mg/dl), did not affect the production of MMP-2/-9, it activated MMP-2 in HB2 cells over-expressing ErbB2 (HB2(ErbB2)), but not HB2 cells; it enhanced the cleavage of proform MMP-2 (72 kDa) to an active form (62 kDa). The activation was dependent on c-jun N-terminal kinases (JNKs) and reactive oxygen species (ROS). On the other hand, ethanol affected neither the expression nor the activation of MMP-9. Selective inhibitors of MMP-2 (SB-3CT and OA-Hy) and antioxidants significantly inhibited ethanol-stimulated invasion of HB2(ErbB2) cells. Furthermore, knocking down MMP-2 by small interference RNA also induced a partial blockage on ethanol-promoted invasion of HB2(ErbB2) cells. Thus, ethanol-stimulated invasion of cells over-expressing ErbB2 was mediated, at least partially, by MMP-2 activation.

Blotting, Western↗

PubMed2006

Essential roles of ERKs and p38K in up-regulation of GST A1 expression by Maotai content in human hepatoma cell line Hep3B.

It is widely accepted that the consumption of alcohol may lead to hepatic injuries such as hepatic fibrosis and cirrhosis. However, consumption of Maotai, one of the famous liquors in China, is found to have no obvious relevance with hepatic injury as ordinary white wine does in both epidemiological and histopathological studies. Present study used human hepatoma cell line Hep3B to address the mechanisms involved in the resistance of alcohol-induced hepatic injury by Maotai liquor. We found that exposure of Hep3B cells to Maotai residue without ethanol (MRWE) resulted in the increased GST A1 anti-oxidant responsive element (ARE) transcriptional expression, while MRWE treatment did not affect Nrf-2-dependent transcriptional activity. Those findings were further confirmed at all time points and doses tested, suggesting that GST A1 transcription was regulated by MRWE via an Nrf-2-independent pathway. Consistent with GST A1 induction, the phosphorylation of c-Jun, extracellular signal-regulated kinases (ERKs) and p38 kinase (p38 K), were also observed in MRWE-treated Hep3B cells. Furthermore, pretreatment of cells with either PD98059 (an inhibitor specific for MEK1/2-ERKs pathway) or SB202190 (an inhibitor specific for p38 K) led to a significant decrease in the induction of GST A1 transcriptional expression by MRWE treatment. Our results indicate that certain content in MRWE is able to induce GST A1 ARE transcriptional expression, which may provide protective effects for hepatic cells by antagonizing the oxidative stress derived from ethanol via an ERKs- and p38 K-dependent pathway.

Alcoholic Beverages↗

PubMed2006

Reactive oxygen species regulate insulin-induced VEGF and HIF-1alpha expression through the activation of p70S6K1 in human prostate cancer cells.

Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of angiogenesis. HIF-1 is composed of HIF-1alpha and HIF-1beta subunits, and regulates VEGF expression at transcriptional level. In this study, we demonstrated that insulin induced H2O2 production and p70S6K1 activation in PC-3 prostate cancer cells. The inhibition of H2O2 production by catalase abolished insulin-induced p70S6K1 activation. H2O2 production is also required for insulin-induced VEGF and HIF-1alpha expression in the cells. Over-expression of p70S6K1 or HIF-1alpha reversed catalase- and rapamycin-inhibited VEGF transcriptional activation. These results suggest that insulin induced HIF-1alpha and VEGF expression through H2O2 production and p70S6K1 activation in prostate cancer cells. In addition, we found that inhibition of p70S6K1 by rapamycin decreased prostate tumor angiogenesis, suggesting that p70S6K1 plays an important role in tumor angiogenesis. These results provide some useful information for prostate cancer therapy in the future.

Animals↗

PubMed2006

Constructing molecular classifiers for the accurate prognosis of lung adenocarcinoma.

PURPOSE: Individualized therapy of lung adenocarcinoma depends on the accurate classification of patients into subgroups of poor and good prognosis, which reflects a different probability of disease recurrence and survival following therapy. However, it is currently impossible to reliably identify specific high-risk patients. Here, we propose a computational model system which accurately predicts the clinical outcome of individual patients based on their gene expression profiles. EXPERIMENTAL DESIGN: Gene signatures were selected using feature selection algorithms random forests, correlation-based feature selection, and gain ratio attribute selection. Prediction models were built using random committee and Bayesian belief networks. The prognostic power of the survival predictors was also evaluated using hierarchical cluster analysis and Kaplan-Meier analysis. RESULTS: The predictive accuracy of an identified 37-gene survival signature is 0.96 as measured by the area under the time-dependent receiver operating curves. The cluster analysis, using the 37-gene signature, aggregates the patient samples into three groups with distinct prognoses (Kaplan-Meier analysis, P < 0.0005, log-rank test). All patients in cluster 1 were in stage I, with N0 lymph node status (no metastasis) and smaller tumor size (T1 or T2). Additionally, a 12-gene signature correctly predicts the stage of 94.2% of patients. CONCLUSIONS: Our results show that the prediction models based on the expression levels of a small number of marker genes could accurately predict patient outcome for individualized therapy of lung adenocarcinoma. Such an individualized treatment may significantly increase survival due to the optimization of treatment procedures and improve lung cancer survival every year through the 5-year checkpoint.

Adenocarcinoma↗

PubMed2006

Phosphatidylinositol 3-kinase/Akt positively regulates Fas (CD95)-mediated apoptosis in epidermal Cl41 cells.

Fas (CD95)-mediated apoptosis is an essential mechanism for the maintenance of homeostasis, and disruption of this death pathway contributes to many human diseases. The cell survival protein kinase Akt/protein kinase B (PKB) is a known regulator of apoptosis, but its role in Fas-mediated cell death and its regulatory mechanisms are unclear. In this study, we show that stimulation of the Fas receptor by its ligand (FasL) induces rapid phosphorylation of Akt/PKB and a parallel increase in cell apoptosis in epidermal Cl41 cells. Inhibition of PI3K/Akt by dominant-negative overexpression of PI3K (Deltap85) and Akt (Akt-T308A/S473A) protects the cells from apoptosis, indicating an unexpected proapoptotic role of PI3K/Akt in the Fas signaling process. Treatment of the cells with pharmacological inhibitors of PI3K, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-1 (LY294002), similarly inhibits FasL-induced apoptosis and Akt/PKB phosphorylation, indicating that PI3K is an upstream mediator of Akt/PKB and is involved in Fas-mediated cell death. Electron spin resonance studies show that FasL treatment induces rapid generation of reactive oxygen species, and inhibition of ROS by antioxidants effectively inhibits Akt/PKB signaling, suggesting that FasL activation of Akt/PKB is redox sensitive. In cells transfected with dominant-negative PI3K/Akt, Fas expression is down-regulated, but FLIP expression is unaffected. Reporter gene and mRNA expression assays show that FasL activates fas transcriptional activity and this effect is inhibited by PI3K/Akt suppression. Together, our results indicate that the PI3K/Akt, in addition to its normal prosurvival role, also plays an apoptotic role in Fas-mediated cell death through a mechanism that involves transcriptional activation of Fas receptor.

Androstadienes↗

PubMed2006

As(III) transcriptionally activates the gadd45a gene via the formation of H2O2.

Arsenic is a ubiquitous environmental contaminant associated with increased risks of human cancers of the skin, lung, bladder, and prostate. Intriguingly, it is also used to treat certain types of leukemia. It has recently been suggested that these paradoxic effects may be mediated by arsenic's ability to simultaneously activate DNA damage and apoptotic and transformation pathways. Here, we investigate the effects of arsenic exposure on the induction of the growth arrest and DNA damage protein 45 alpha (GADD45 alpha), which is thought to play roles in apoptosis, DNA damage response, and cell cycle arrest. We found that arsenic transcriptionally activates the gadd45 alpha promoter located in a 153-bp region between -234 and -81, relative to the transcriptional start site. In addition, this transcriptional induction was abrogated in the presence of H2O2 scavengers, suggesting a role for H2O2 in the transcriptional control of the gadd45a gene through a Fenton-like free radical mechanism.

Arsenic↗

PubMed2006

Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity.

Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo.

Animals↗

PubMed2006

Actions of a histone deacetylase inhibitor NSC3852 (5-nitroso-8-quinolinol) link reactive oxygen species to cell differentiation and apoptosis in MCF-7 human mammary tumor cells.

NSC3852 (5-nitroso-8-quinolinol) has cell differentiation and antiproliferative activity in human breast cancer cells in tissue culture and antitumor activity in mice bearing P388 and L1210 leukemic cells. We investigated the mechanism of NSC3852 action in MCF-7 human breast cancer cells using electron spin resonance (ESR). Reactive oxygen species (ROS) were detected in MCF-7 cell suspensions incubated with NSC3852 using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Formation of the DMPO-OH adduct was quenched by the addition of superoxide dismutase but not by catalase, and we concluded that superoxide was generated in the NSC3852-treated cells. The flavoprotein inhibitor diphenylene iodonium suppressed ROS production, providing evidence for the involvement of a flavin-dependent enzyme system in the ROS response to NSC3852. A biologically significant oxidative response to NSC3852 occurred in MCF-7 cells. An early marker of oxidative stress was a decrease in the [glutathione]/[glutathione disulfide] ratio 1 h after NSC3852 addition. Oxidative DNA damage, marked by the presence of 8-oxoguanine, and DNA-strand breakage occurred in cells exposed to NSC3852 for 24 h. Apoptosis peaked 48 h after exposure to NSC3852. Pretreatment with the glutathione precursor N-acetyl-l-cysteine (NAC) prevented DNA-strand breakage and apoptosis. Pretreatment with NAC also reversed NSC3852 decreases in E2F1, Myc, and phosphorylated retinoblastoma protein, indicative of redox-sensitive pathway(s) in MCF-7 cells during G(1) phase of the cell cycle. We conclude that ROS formation is involved in the apoptotic and cell differentiation responses to NSC3852 in MCF-7 cells.

Apoptosis↗

PubMed2006

Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA.

The present study shows that arsenic induces GADD45alpha (growth arrest and DNA damage inducible gene 45alpha) mainly through post-transcriptional mechanism. Treatment of the human bronchial epithelial cell line, BEAS-2B, with arsenic(III) chloride (As3+) resulted in a significant increase in GADD45alpha protein and mRNA. However, As3+ only exhibited a marginal effect on the transcription of the GADD45alpha gene. The accumulation of GADD45alpha mRNA is largely achieved by the stabilization of GADD45alpha mRNA in the cellular response to As3+. As3+ is able to induce binding of mRNA stabilizing proteins, nucleolin and less potently, HuR, to the GADD45alpha mRNA. Although As3+ was unable to affect the expression of nucleolin, treatment of the cells with As3+ resulted in re-distribution of nucleolin from nucleoli to nucleoplasm. Silencing of the nucleolin mRNA by RNA interference reversed As3+-induced stabilization of the GADD45alpha mRNA and accumulation of the GADD45alpha protein. Stabilization of GADD45alpha mRNA, thus, represents a novel mechanism contributing to the production of GADD45alpha and cell cycle arrest in response to As3+.

Arsenicals↗

PubMed2006

Inhibition of benzo(a)pyrene-induced cell cycle progression by all-trans retinoic acid partly through cyclin D1/E2F-1 pathway in human embryo lung fibroblasts.

Benzo(a)pyrene [B(a)P] is a potent environmental carcinogen, which induces cell cycle changes. All-trans retinoic acid (ATRA) is a promising agent in prevention and treatment of human cancers. In the present study, we investigated the inhibition of B(a)P-induced cell cycle progression by ATRA in human embryo lung fibroblast (HELF). Our results showed that after treatment with B(a)P, the expression of cyclin D1 and E2F-1 were both increased significantly in HELF. There were almost no changes of CDK4 and E2F-4 expression by treatment with B(a)P. As expected, pretreatment with ATRA could efficiently decrease B(a)P-induced overexpression of cyclin D1 and E2F-1. In a further study, we stably transfected antisense cyclin D1 and antisense CDK4 plasmid into HELF. The inhibition of cyclin D1 expression and the inhibition of CDK4 expression significantly impaired the B(a)P-induced overexpression of E2F-1 respectively. Pretreatment with ATRA, cells expressing antisense cyclinD1 or antisense CDK4 showed a lesser decrease of B(a)P-induced overexpression of E2F-1 compared with similarly treated HELF. Furthermore, flow cytometry analysis showed that B(a)P promoted cell cycle progression from G(1) phase to S phase, while pretreatment with ATRA could inhibit B(a)P-induced cell cycle progression by an accumulation of cells in the G(1) phase. It was suggested that ATRA could block B(a)P-induced cell cycle promotion partly through the cyclin D1/E2F-1 pathway in HELF.

Benzo(a)pyrene↗

PubMed2006

Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression.

Recent studies demonstrate that PI3K activation and PTEN mutation are frequently found in many human cancer cells and tissues. However, the mechanism of PI3K signaling in human cancer tumorigenesis remains to be elucidated. In this study we specifically downregulated p110alpha expression in ovarian cancer cells using siRNA interference. We found that p110alpha downregulation greatly decreased ovarian tumor growth and angiogenesis, and that p110alpha siRNA inhibited VEGF expression through decreasing hypoxia-inducible factor 1alpha expression in both ovarian cancer cells and tumor tissues. To determine the downstream targets of PI3K in regulating tumor growth and angiogenesis, we find that AKT1 is a major downstream mediator for regulating tumor growth, angiogenesis, and VEGF expression. These data show that p110alpha and AKT1 play an important role in tumor growth by inducing angiogenesis and by increasing HIF-1alpha and VEGF expression. This work provides a better understanding of the molecular mechanism of human cancer induced by the activation of PI3K signaling.

Animals↗

PubMed2006

Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells.

Inflammation and oxidative stress are associated with cancer, atherosclerosis, and other chronic diseases. Dietary flavonoids have been reported to possess antiinflammatory and antioxidant properties, but their mechanisms of action and structure-activity relations have not been fully investigated. We hypothesized that differences in antioxidant activity between the structurally similar flavones, luteolin and chrysin (differing only in B-ring hydroxylation patterns), would differentially affect inflammation-associated Cox-2 expression and PGE2 formation. Pretreatment of RAW 264.7 macrophage-like cells with 25, 50, or 100 micromol/L concentrations of luteolin inhibited lipopolysaccharide (LPS)-induced Cox-2 protein expression (P < 0.0001). Chrysin pretreatment did not reduce LPS-induced Cox-2 protein expression at any level tested. Conversely, both luteolin and chrysin completely suppressed LPS-induced PGE2 formation (P < 0.001). Luteolin, but not chrysin, inhibited xanthine/xanthine oxidase-generated superoxide formation at 100 micromol/L in a cell-free system (P < 0.001). Although both luteolin and chrysin reduced LPS-induced hydroxyl radical formation relative to the positive control (P < 0.001), luteolin was superior to chrysin (P = 0.003). In summary, luteolin and chrysin suppressed PGE2 formation equally well, despite differential effects on Cox-2 protein expression and on superoxide and hydroxyl radical scavenging. These data indicate that flavones may display similar antiinflammatory activity via different mechanisms.

Cell Survival↗

PubMed2006

Alcohol-induced oxidative stress and cell responses.

Epidemiological and animal studies have demonstrated that alcohol abuse is directly associated with the increase of multiple organ diseases, such as liver injury, cardiovascular diseases, and neurological disorders. While the mechanisms of alcohol-induced cell injury and disease remain to be investigated, recent studies indicate that reactive oxygen species (ROS) may play an important role. Reactive oxygen species are able to cause various cellular injuries, such as DNA damage, lipid peroxidation and protein modification. Cellular systems are protected from ROS-induced cell injuries by an array of defenses composed of various anti-oxidants with different functions. When the ROS present in the cellular system overpower the defense systems, they will cause oxidative stress or cell injury, leading to the development of diseases. This article reviews recent literature on alcohol-induced ROS production, oxidative stress, signal transduction, and cellular responses. The implication of these processes in alcohol-related diseases is also discussed.

Alcohol-Related Disorders↗