Biomedical subjects

T Y Liu

Publications and source records attributed to T Y Liu.

At least 55 records · Page 3Linked to original sources

PubMed1999

On the biosynthesis of alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid catalyzed by the sialyltransferase of Escherichia coli Bos-12.

Escherichia coli Bos-12 synthesizes a heteropolymer of sialic acids with alternating alpha-2,9/alpha-2,8 glycosidic linkages (1). In this study, we have shown that the polysialyltransferase of the E. coli Bos-12 recognizes an alpha-2,8 glycosidic linkage of sialic acid at the nonreducing end of an exogenous acceptor of either the alpha-2,8 homopolymer of sialic acid or the alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid and catalyzes the transfer of Neu5Ac from CMP-Neu5Ac to this residue. When the exogenous acceptor is an alpha-2,8-linked oligomer of sialic acid, the main product synthesized is derived from the addition of a single residue of [14C]Neu5Ac to form either an alpha-2,8 glycosidic linkage or an alpha-2,9 glycosidic linkage at the nonreducing end, at an alpha-2, 8/alpha-2,9 ratio of approximately 2:1. When the acceptor is the alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid, chain elongation takes place four to five times more efficiently than the alpha-2,8-linked homopolymer of sialic acid as an acceptor. It was found that the alpha-2,9-linked homopolymer of sialic acid and the alpha-2,8/alpha-2,9-linked hetero-oligomer of sialic acid with alpha-2,9 at the nonreducing end not only failed to serve as an acceptor for the E. coli Bos-12 polysialyltransferase for the transfer of [14C]Neu5Ac, but they inhibited the de novo synthesis of polysialic acid catalyzed by this enzyme. The results obtained in this study favor the proposal that the biosynthesis of the alpha-2, 9/alpha-2,8 heteropolymer of sialic acid catalyzed by the E. coli Bos-12 polysialyltransferase involves a successive transfer of a preformed alpha-2,8-linked dimer of sialic acid at the nonreducing terminus of the acceptor to form an alpha-2,9 glycosidic linkage between the incoming dimer and the acceptor. The glycosidic linkage at the nonreducing end of the alternating alpha-2,9/alpha-2,8 heteropolymer of sialic acid produced by E. coli Bos-12 should be an alpha-2,8 glycosidic bond and not an alpha-2,9 glycosidic linkage.

Carbohydrate Conformation↗

PubMed1999

Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells.

BACKGROUND: Berberine, one of the major constitutents of alkaloids of Coptis chinensis is frequently utilized in the treatment of inflammation and liver-related diseases. In Chinese herbal medicine, Coptis chinensis is used as a prophylactic drug to treat gastrointestinal disorders. In a previous study, the authors found that berberine reduced cell proliferation and alpha-fetoprotein expression in human hepatoma HepG2 cells. Multidrug resistance transporter (pgp-170) is known to be overexpressed in HepG2 cells. Whether berberine regulates the expression of pgp-170 in HepG2 and other hepatoma cell lines is unknown and worthy of investigation. METHODS: Human and murine hepatoma cells were treated with berberine (0.32, 3.2, 32, and 320 microM), tamoxifen (1 microM), or verapamil (10 microM) for 24 hours. Flow cytometry was used to measure retention of a fluorescence dye, rhodamine 123, and the level of immunoreactive pgp-170 in berberine-treated hepatoma cells. RESULTS: Berberine up-regulated the expression of pgp-170 in three human hepatoma cell lines. The function of pgp-170 was blocked by tamoxifen and verapamil, resulting in increased retention of rhodamine 123. Retention of rhodamine 123 was significantly reduced in berberine-treated hepatoma cells. CONCLUSIONS: Berberine modulates the expression and function of pgp-170 in hepatoma cells. These results suggest that treatment of tumor cells with berberine may result in reduced retention of chemotherapeutic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Singlet oxygen is the major species participating in the induction of DNA strand breakage and 8-hydroxydeoxyguanosine adduct by lead acetate.

To investigate DNA damage induced by Pb2+ and its prevention by scavengers, we determined DNA strand breakage and the formation of 8-hydroxydeoxyguanosine (8-OHdG) in DNA using plasmid relaxation assay and HPLC with electrochemical detection, respectively. Lead acetate induced DNA strand breakage in 10 mM of Hepes buffer, pH 6.8, in a time- and dose-dependent manner. Compared with lead, zinc acetate did not significantly induce DNA breakage. The singlet oxygen scavengers NaN3 and 2,2,6,6-tetramethyl-4-piperidone (TEMP) inhibited lead-induced DNA breakage more efficiently than the hydroxyl radical scavengers mannitol and DMPO. Deuterium oxide (D2O), a singlet oxygen enhancer, potentiated lead-induced DNA breakage. At low ratios to Pb2+, NADPH, glutathione, and 2-mercaptoethanol enhanced lead-induced DNA breakage, whereas high ratios of these agents protected it. Catalase and superoxide dismutase (SOD) did not protect DNA breaks induced by Pb2+. Lead-induced DNA breakage was markedly enhanced by H2O2, and this induction was inhibited by NaN3, TEMP, EDTA, catalase, BSA, and glutathione. In contrast, mannitol and SOD potentiated Pb2+/H2O2-induced DNA breaks. The results indicate that singlet oxygen, lead, and H2O2 are all involved in the reaction system, whereas hydroxyl radical and superoxide did not. Lead could cause a small amount of 8-OHdG formation in calf thymus DNA and dose-dependently induced the formation of this adduct in the presence of H2O2. Singlet oxygen scavengers were more effective than hydroxyl radical scavengers in protection from lead/H2O2-induced 8-OHdG adducts. Taken together, these results suggest that lead may induce DNA damage through a Fenton-like reaction and that singlet oxygen is the principal species involved.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Safrole-induced oxidative damage in the liver of Sprague-Dawley rats.

Safrole is a weak hepatocarcinogen, and its carcinogenic effect has been linked to the formation of stable safrole DNA adducts. In this study, we tested whether safrole also induces oxidative damages in Sprague-Dawley rats. By single i.p. injection, safrole dose-dependently induced the formation of hepatic lipid hydroperoxides (LHP) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). The safrole-induced LHP reached peak level on day 3 and gradually returned to the basal level on day 15. On the other hand, 8-OH-dG levels from the similarly treated rats peaked on day 5 and returned to basal level on day 15. Safrole also dose-dependently induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. We also examined the protective effect of vitamin E, deferoxamine and N-acetylcysteine against the safrole-induced oxidative damage. N-Acetylcysteine, the precursor of glutathione, exerted the greatest protective effect among the three antioxidants tested. In contrast, buthionine sulfoximine, the glutathione synthesis inhibitor, enhanced the safrole-induced oxidative damage, as evidenced by the elevation of LHP and 8-OH-dG levels on day 3 (P<0.05). These findings demonstrate that safrole treatment induces oxidative damage in rat hepatic tissue, and glutathione plays an important protective role. This oxidative damage may be involved in the hepatocarcinogenic effect of safrole.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel.

Berberine is the major constituent of Coptis chinese and is commonly used in Chinese herbal medicine to treat patients with gastrointestinal disorders. In this study, using flow cytometry, we have found that a 24-h berberine treatment up-regulated the multidrug-resistant transporter (pgp-170) expression in two oral (KB, OC2), two gastric (SC-M1, NUGC-3) and two colon (COLO 205, CT 26) cancer cell lines. Decreased retention of rhodamine 123 was observed in berberine-treated cells as compared to vehicle control. To examine whether the berberine modulated pgp-170 expression in cancer cells is associated with changes in drug resistance, we determined the cytotoxicity, cell cycle progression and cell morphology of Paclitaxel-treated cells. Paclitaxel (1 nM-10 microM) treatment for 24 h induced cytotoxicity in OC2, SC-M1 and COLO 205 cells in a dose-dependent manner. Pretreatment of cells with 32 microM berberine for 24 h prior to Paclitaxel treatment resulted in increased viability as compared to that of Paclitaxel-treated cells. In addition, Paclitaxel-induced apoptosis and/or G2/M arrest in these three cancer cell lines. Pretreatment of cells with berberine prior to Paclitaxel blocked the Paclitaxel-induced cell cycle responses and morphological changes. These results together suggest that berberine modulated the expression and function of pgp-170 that leads to reduced response to Paclitaxel in digestive track cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history.

Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betel inflorescence, which contains 15 mg/g safrole, is a unique ingredient of BQ in Taiwan. Chewing such prepared BQ may contribute to safrole exposure in human beings (420 microM safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a (32)P-post-labeling method, we have found a high frequency of safrole-like DNA adducts in BQ-associated OSCC (77%, 23/30) and non-cancerous matched tissue (NCMT) (97%, 29/30). This was in contrast to the absence (< 1/10(9) nucleotides) of such adducts in all of non-BQ-associated OSCC and their paired NCMT (P < 0.001). Six of seven OSF also exhibited the same safrole-like DNA adduct. The DNA adduct levels in OSF and NCMT were significantly higher than in OSCC (P < 0.05). Using co-chromatography and rechromatography techniques, we further demonstrated that these adducts were identical to synthetic safrole-dGMP adducts as well as DNA adducts from 1'-hydroxysafrole-treated HepG2 cells. These results suggest that safrole forms stable safrole-DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis.

Areca↗

PubMed1999

No association between alpha-1-antichymotrypsin polymorphism and Alzheimer's disease in Chinese.

A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) confers a significant risk for Alzheimer's disease (AD). Furthermore, the apolipoprotein E epsilon4 allele (APOE*4) effect associated with AD risk is modified by the ACT polymorphisms. To evaluate the role of ACT polymorphism in AD, we conducted an association study of ACT polymorphisms in Chinese AD patients and normal controls. We found that the ACT polymorphism had no effect on the development of AD either alone or in combination with the APOE*4 allele.

Aged↗

PubMed1998

Induction of pulmonary fibrosis in organ-cultured rat lung by cadmium chloride and transforming growth factor-beta1.

Cadmium chloride (CdCl2) exposure has been reported to induce pulmonary fibrosis in rats. Accumulating evidence has shown that cytokines play a pivotal role in the excessive production of connective tissue components in pulmonary fibrosis. In this report, rat lung slice cultures were used to study the synergistic involvement of transforming growth factor-beta1 (TGF-beta1) in CdCl2-induced alveolar fibrosis. Rat lung slices were maintained at the interphase of air and medium on a polyester mesh stretched on a plastic scaffold. Treatment of lung slices with 2.5, 5 or 10 microM CdCl2 for 7 days resulted in 85, 40 and 6% respectively for relative survival. Under these culture conditions, CdCl2 alone did not induce alveolar fibrosis in rat lung slices. However, in the presence of 0.5 ng/ml TGF-beta1, CdCl2 at a dose ranging from 1 to 5 microM increased the thickness of alveolar septa. Furthermore, the thickness of alveolar septa in lung slices treated with CdCl2 was dose-dependently increased by the presence of TGF-beta1. The thickened alveolar septa were apparently due to the deposition of excessive extracellular matrix, as revealed by trichrome stain and ultrastructural examination. Our results also show that fibrogenic activity induced by the combined treatment with CdCl2 and TGF-beta1 can be reduced by co-treatment with 200 microg/ml lambda-carrageenan, a TGF-beta1 inhibitor. Therefore, the present results indicate that TGF-beta1 can synergistically stimulate the fibrogenic activity in lung tissue subsequent to CdCl2 injury.

Animals↗

PubMed1998

p53 alterations in betel quid- and tobacco-associated oral squamous cell carcinomas from Taiwan.

Alterations of p53 have been explored in Taiwanese oral squamous cell carcinomas (OSCCs) consisting of a betel quid (BQ)/tobacco-related subgroup of 36 subjects and a tobacco-related subgroup of 13 subjects. Mutations in conserved exons were found in 12 tumors. Seven mutations were clustered in a hot-spot region mapped to a region between codons 273-282 in exon 8. The incidence of p53 mutation in BQ/tobacco tumors was 22% (8/36). The frequency of p53 allelic loss (21%, 3/14) in BQ/tobacco tumors approximates to the incidence of mutation. This is the first study demonstrating allelic deletion of p53 in such malignancies. Twenty-four of 43 samples showed positive p53 immunostaining. All tumors harboring mis-sense mutations of p53 in conserved exons exhibited nuclear protein accumulation. The incidence of mutation in conserved exons in BQ/tobacco-associated Asian OSCCs (15%) is significantly different from worldwide OSCCs (46%) related primarily to tobacco consumption (P=0.00001).

Adult↗

PubMed1998

In vitro and in vivo growth inhibition of cancer cells by adamantylmaleimide derivatives.

We have previously found that adamantylmaleimide derivatives inhibited the growth of several cancer cell lines in vitro. In this study we examined the effect of adamantylmaleimide derivatives on the in vivo and in vitro growth of human gastric cancer cells. Experimental results showed that N-1-adamantylmaleimide (AMI) and N-1-(3,5-dimethyladamantyl)maleimide (DMAMI) exert modest growth inhibitory activities in vitro against five different cancer cell lines. In contrast, N-1-(3,5-dimethyl-adamantyl)maleamic acid (DMAMA), N-1-adamantylmaleamic acid (AMA) and N-1-adamantylsuccinimide (ASI) were virtually inactive. These results suggest that the double bond of N-substituted maleimide plays a prominent role in their antitumor activities. Further analysis with flow cytometry showed an accumulation of apoptotic SC-M1 cells after treatment with 3-10 microM AMI or 5-20 microM DMAMI for up to 72 h. DNA fragmentation by gel electrophoresis confirmed that AMI- and DMAMI- induced cytotoxicity led to cell apoptosis. In addition, scanning electron microscopy (SEM) showed that treating cells with AMI (> or = 10 microM) for 24 h, significantly changed the morphology of SC-M1 cells, i.e. they had an irregular flat shape and the cell membrane was porous. The AMI-induced morphological changes of the cell membrane may lead to apoptosis of SC-M1 cells. AMI-induced growth inhibition was observed in vivo using SCID mice bearing SC-M1 tumors. The AMI-induced growth inhibition of SC-M1 tumor was dose-dependent.

Adamantane↗

PubMed1997

Seroprevalences of hepatitis B and C viruses and Helicobacter pylori infection in a small, isolated population at high risk of gastric and liver cancer.

The objective of this study was to examine the seroprevalences of chronic infection with hepatitis B and C viruses and Helicobacter pylori in Matzu, a group of small islets with 5,566 civilian residents who have extremely high mortality from cancers of the stomach and liver. The standardized mortality ratios (SMR) of all cancer sites combined, liver cancer and stomach cancer in 1984-1993 were calculated using the general population in Taiwan as the referent (SMR = 100). The SMRs (95% confidence interval) for all cancer sites combined, liver cancer and stomach cancer were 160 (131-195), 252 (170-360) and 351 (229-516), respectively, in Matzu. A health survey was carried out with 1,485 civilian residents aged 30 years or more, giving a response rate of 69% among those who were eligible. Serum samples were tested for antibodies against Helicobacter pylori (anti-HP) by enzyme-linked immunosorbent assay and hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) by enzyme immunoassay. The seroprevalence was 61% for anti-HP, 24.7% for HBsAg and 1.8% for anti-HCV in Matzu. While mortality rates of liver and stomach cancers were significantly higher in Matzu than in Taiwan, the seroprevalences of anti-HP, HBsAg and anti-HCV in Matzu were similar to or even lower than those in Taiwan. These findings suggest the existence of risk factors other than microbial agents involved in the development of stomach and liver cancers.

Adult↗

PubMed1996

Modification of mitomycin C-induced clastogenicity by Terminalia catappa L. in vitro and in vivo.

The water extract of the leaves of Terminalia catappa L. was tested for inhibition of mitomycin C-induced micronuclei in CHO-K1 cells. The simultaneous and pre-treatment of CHO-K1 cells with T. catappa extract (75 and 150 micrograms/ml) significantly (P < 0.05) suppressed mitomycin C-induced micronuclei. Furthermore, gastric intubation of T. catappa extract (4.8 and 24 mg/animal per day) to male ICR mice for 8 days significantly (P < 0.01) reduced mitomycin C-induced micronuclei in peripheral blood. In addition, T. catappa dose dependently inhibited lipid peroxidation in vitro and TPA-induced hydrogen peroxide formation in human mononuclear leukocytes. The anticlastogenic effects of T. catappa in vitro and in vivo may be attributed to its antioxidative potential.

Animals↗

PubMed1996

Paclitaxel-induced apoptosis in human gastric carcinoma cell lines.

BACKGROUND: Gastric cancer is one of the most common cancers in Asia. Chemotherapy and radiation therapy have had limited success. Recently, paclitaxel has been found to be effective against a variety of cancers, including lung, breast, ovary, melanoma, and prostate. Whether paclitaxel is effective in the treatment of gastric cancer is not known and is worthy of investigation. METHODS: Human gastric carcinoma cell lines NUGC-3 and SC-M1 were examined for response to paclitaxel treatment. Cancer cells were treated with paclitaxel (0.001, 0.01, 0.1, and 1 microM) for 1-3 days. Cell number was counted by hemocytometer and cell viability was determined by the trypan blue exclusion method. Cell cycle progression and expression of proliferating cell nuclear antigen (PCNA) were examined by flow cytometry. The percentage of apoptotic cells was determined after staining with hematoxylin and eosin. RESULTS: Paclitaxel was cytotoxic to the two human gastric carcinoma cell lines examined. The growth-inhibiting dose was 0.01 microM. Paclitaxel-treated gastric carcinoma cells were arrested mainly in G2/M phases before apoptosis. However, treatment with 0.01 microM of paclitaxel resulted in a decrease of cells at G0/G1 phases without an increase of cells at G2/M phase indicating that paclitaxel was also cytotoxic to gastric carcinoma cells at G0/G1 phases. In addition, the expression of PCNA was significantly increased in 0.1 and 1 microM paclitaxel-treated cells, suggesting that DNA repair was increased in these cells. CONCLUSIONS: Paclitaxel is effective in growth inhibition of gastric carcinoma cell lines in clinically attainable concentrations. Our results suggest that paclitaxel is a potential chemotherapeutic drug for gastric carcinoma.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Oxidative damage to DNA induced by areca nut extract.

In Taiwan, people chew betel quid which contains tender areca nut with husk. In other countries, people prefer ripe and dried areca nut without husk. In this study, we compared the reactive oxygen species-induced oxidative DNA damage in isolated DNA and CHO-K1 cells between treatments with tender areca nut extract (ANE) and ripe ANE. Incubation of these two ANE preparations with isolated DNA generated 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in an alkaline environment in a dose-dependent manner. Ripe ANE generated higher levels of 8-OH-dG compared to tender ANE. The addition of iron(II) (100 microM) resulted in 1.4- and 3.1-fold increases of 8-OH-dG when incubated with 1 mg/ml each of tender and ripe ANE. In testing the effect of ANE to cellular DNA, CHO-K1 cells were used for its documented sensitivity to reactive oxygen species. In CHO-K1 cells, ripe ANE was more cytotoxic than tender ANE following an 18-h incubation. The cytotoxicity to CHO-K1 cells was positively correlated with the formation of 8-OH-dG following tender (r=0.97) and ripe (r=0.91) ANE treatment. Addition of the iron chelating agent o-phenanthroline (10 and 20 microM) to cells prior to ri ANE exposure significantly increased (p<0.05) the survival of CHO-K1 cells. In addition, ripe ANE induced dichlorofluorescein-mediated fluorescence which indicated the formation of hydrogen peroxide in CHO-K1 cells. In conclusion, this study demonstrated that ANE-induced oxidative damage to isolated and cellular DNA which may result from the generation of hydrogen peroxide, and iron may serve as a catalyst in this process. Furthermore, ripe ANE generated higher oxidative DNA damage levels compared to tender ANE.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Induction of 8-hydroxydeoxyguanosine in DNA by chromium(III) plus hydrogen peroxide and its prevention by scavengers.

The capability of Cr(III) to induce DNA lesions generated by oxidative damage was investigated in this study by examining the formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA by CrCl3 and/or H2O2 in 10 mM phosphate buffer. In the presence of 0.5 mM H2O2, the formation of 8-OHdG markedly increased with increasing CrCl3 concentration. In contrast, H2O2 or CrCl3 alone did not cause any increase in 8-OHdG level above background. The amount of 8-OHdG induced by CrCl3 plus H2O2 was time dependent; its generation increased linearly over an incubation period of 90 min. The formation of 8-OHdG was unfavorable in an acidic solution (pH < 6); the highest level of 8-OHdG was observed at pH 7-8. Scavengers of reactive oxygen species markedly inhibited the formation of 8-OHdG by CrCl3 plus H2O2; the inhibition effect was sodium azide > D-mannitol > Tris-HCl at an equal concentration. The induction of 8-OHdG by CrCl3 plus H2O2 remained unchanged in D2O. Moreover, an addition of catalase (2.2 U/ml) to the reaction mixture completely inhibited the formation of 8-OHdG by CrCl3/H2O2, whereas only 22% of that formation was inhibited by superoxide dismutase (11 U/ml). A large amount of bovine serum albumin (1.1 mg/ml) could reduce the formation of 8-OHdG by CrCl3 plus H2O2, thereby implying that Cr(III)-mediated DNA-protein crosslinks are unfavorable for 8-OHdG formation. Furthermore, ascorbate could prevent the formation of 8-OHdG by CrCl3 plus H2O2; the extent of prevention increased with increasing ascorbate concentration (10 microM-3 mM). Thus, ascorbate acts as a free radical scavenger in the CrCl3/H2O2 system. The above findings suggest that Cr(III)/H2O2 could generate oxidative damage to DNA, possibly through a Fenton-like reaction, i.e. Cr(III)+H2O2-->Cr(IV)+.OH+OH-. This study also indicates that Cr(III), previously considered as the ultimate kinetically stable species of Cr(VI) metabolites, is capable of inducing carcinogenic lesions through interaction with a cellular oxygen species.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Role of oxidative DNA damage in hydroxychavicol-induced genotoxicity.

Chewing betel quid has been linked to the development of oral cancer. In Taiwan, fresh Piper betle inflorescence is uniquely added to betel quid, and hydroxychavicol is the major phenolic components of P.betle inflorescence. In this study, we tested the mutagenic potential of hydroxychavicol in Salmonella typhimurium TA97, TA98, TA100 and TA102 with and without Aroclor-1254 induced S9 fraction. The results showed that hydroxychavicol was positive in S.typhimurium TA102 without metabolic activation. This increase in revertants was partially inhibited by catalase and superoxide dismutase. In Chinese hamster ovary (CHO-K1) cells, hydroxychavicol induced chromosome aberrations in a dose-dependent manner (10-50 microM) and the majority were chromosome-type aberrations. Hydroxychavicol also significantly increased the frequency of micronuclei in CHO-K1 cells up to 3-fold at a concentration of 40 microM. In addition, hydroxychavicol dose-dependently (0.1-20 microM) induced copper-dependent strand breaks in plasmid DNA. We further tested the oxidative DNA damage potential of hydroxychavicol by measuring 8-hydroxydeoxyguanosine (8-OH-dG) formation in CHO-K1 cells following an 18-h incubation and found that hydroxychavicol (6.25-100 microM) induced 8-OH-dG levels dose-dependently. The increase of 8-OH-dG formation was positively correlated (r = 0.79) with the hydroxychavicol-induced cytotoxicity. In conclusion, hydroxychavicol may exert its genotoxic potential through oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Epsilon 4 allele of apolipoprotein E increases risk of Alzheimer's disease in a Chinese population.

We examined the apolipoprotein E genotype in 56 Chinese patients with late-onset sporadic Alzheimer's disease (AD) and 57 Chinese control subjects of similar age. The frequency of epsilon 4 in the AD group was significantly higher than that in the control group (23.2% versus 7.9%, p = 0.003). The odds ratio for AD in individuals with either one or two epsilon 4 was 2.96 (95% CI 1.11 to 8.03). The linear trend for AD in proportion to alleles of epsilon 4 was also significant (chi 2 = 8.2, p = 0.004). Our results support the association between epsilon 4 and AD in the Chinese.

Age of Onset↗

PubMed1995

Heterologous desensitization of opioid-stimulated Ca2+ increase by bradykinin or ATP in NG108-15 cells.

Leucine-enkephalin (Leu-EK) dose-dependently elicited an increase in cytosolic Ca2+ concentration ([Ca2+]i) with an EC50 of 1.2 microM via the phosphoinositide cascade in NG108-15 cells. Chronic treatment of cells with [D-Ala2,D-Leu5]enkephalin caused time-dependent homologous desensitization. In the presence of extracellular Ca2+, ATP as well as bradykinin stimulated significantly higher increases in inositol 1,4,5-trisphosphate (IP3) generation than did Leu-EK; however, the magnitude of intracellular Ca2+ pools increased after ATP stimulation, whereas bradykinin depleted intracellular pools. Hence, cells lost their [Ca2+]i response to Leu-EK if bradykinin was first added to induce a [Ca2+]i increase, whereas the response was unchanged if Leu-EK was added after addition of ATP. When Leu-EK was added simultaneously with bradykinin or ATP, an additive response was observed in IP3 generation; however, the rise in [Ca2+]i reached the same level as that induced by bradykinin or ATP alone. In the absence of extracellular Ca2+ in which the replenishment of intracellular pools was not possible, ATP displayed an inhibitory effect similar to that of bradykinin on the Leu-EK-induced [Ca2+]i increase. Prior treatment of cells with Leu-EK slightly heterologously desensitized the action of bradykinin, but had no effect on the ATP response. Our results suggest that a shared intracellular Ca2+ pool is sensitive to the opioid, bradykinin and P2-purinoceptor agonists; however, a defined pool of phosphatidylinositol 4,5-bisphosphate or a specific phospholipase C is responsible for each receptor.

Adenosine Triphosphate↗