Biomedical subjects

S Y Lin-Shiau

Publications and source records attributed to S Y Lin-Shiau.

At least 91 records · Page 5Linked to original sources

PubMed1997

Zinc, copper, and superoxide dismutase in hepatocellular carcinoma.

Superoxide dismutase (Cu/Zn), a metalloenzyme, activity was found to be significantly lower in the human hepatocellular carcinoma (hepatoma tissue) (0.78 +/- 0.33 U/microg protein) compared with that seen in the surrounding "normal" or cirrhotic tissue (1.40 +/- 0.48 U/microg; 1.27 +/- 0.64 U/microg). The SOD activity of "normal" appearing liver cells adjacent to the tumor or cirrhotic tissue is still lower than that level observed in the normal liver from the subjects without known liver disease (1.40 +/- 0.48 U/microg vs 2.94 +/- 1.53 U/microg). We have also observed that the trace elements of zinc and copper, which are essential in expressing the enzyme activity are also significantly lower in the hepatoma (22.54 +/- 6.73 microg and 2.83 +/- 1.16 microg per gram of tissue) compared with those in the surrounding "normal" hepatic tissue (Zn2+, 64.36 +/- 9.17 microg/g; Cu2+, 11.43 +/- 4.74 microg/g). The difference in the zinc content between the "normal" and the cirrhotic tissue is also significant (64.36 +/- 9.17 microg/g vs 42.37 +/- 10.97 microg/g). However, the copper content in the cirrhotic tissue is higher but not statistically different from that level in the "normal" tissue (15.53 +/- 5.90 microg/g vs 11.43 +/- 4.74 microg/g). Furthermore, the plasma zinc level is significantly lower among the patients who have suffered from hepatoma compared with those subjects without known liver disease (631.73 +/- 52.43 microg/L vs 845.53 +/- 68.13 microg/L). Our data suggest that the superoxide dismutase activity is impaired in the hepatoma tissue. The lower concentration of trace elements (Zn2+ and Cu2+) found in the hepatoma tissue may contribute to cause the difference in the observed enzymic activities.

Adult↗

PubMed1997

Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin.

Apigenin, a less-toxic and non-mutagenic flavonoid, suppressed 12-0-tetradecanoyl-phorbol-13-acetate-(TPA)-mediated tumor promotion of mouse skin. TPA had the ability to activate protein kinase C (PKC) and induced nuclear proto-oncogene expression. Our study indicates that apigenin inhibited PKC by competing with adenosine triphosphate (ATP). Apigenin also reduced the level of TPA-stimulated phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos expression. Curcumin, a dietary pigment phytopolyphenol, is also a potent inhibitor of tumor promotion induced by TPA in mouse skin. When mouse fibroblast cells were treated with TPA alone, PKC translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 microM curcumin for 15 min inhibited TPA-induced PKC activity in the particulate fraction by 26-60%. Curcumin also inhibited PKC activity in vitro by competing with phosphatidylserine. Curcumin (10 microM) suppressed the expression of c-jun in TPA-treated cells. Fifteen flavonoids were examined for their effects on morphological changes in soft agar and cellular growth in v-H-ras transformed NIH3T3 cells. The results demonstrated that only apigenin, kaempferol, and genistein exhibited the reverting effect on the transformed morphology of these cells. Based on these findings, it is suggested that the suppression of PKC activity and nuclear oncogene expression might contribute to the molecular mechanisms of inhibition of TPA-induced tumor promotion by apigenin and curcumin.

Animals↗

PubMed1996

Ischemia-induced alteration of myocardial Na(+)-K(+)-ATPase activity and ouabain binding sites in hypercholesterolemic rabbits.

The purpose of this study was to explore the effect of ischemia on the Na(+)-K(+)-ATPase activity and ouabain receptor of the myocardial sarcolemma in hypercholesterolemic rabbits. Male New Zealand white rabbits were fed with either standard chow or standard chow supplemented with 0.5% (w/w) cholesterol and 10% (w/w) coconut oil. After an 8 week feeding period, the rabbits underwent a thoracotomy and myocardial ischemia was induced by occlusion of the coronary artery. Myocardial samples from the ischemic and non-ischemic regions of the left ventricle of control and cholesterol-fed rabbits were taken for study. The cholesterol-fed group showed a decrease in both Na(+)-K(+)-ATPase activity and [3H]ouabain binding sites as compared to the control group. Ischemia caused a reduction in both Na(+)-K(+)-ATPase activity [3H]ouabain bindings sites in both control and cholesterol-fed rabbits. The combination of ischemia and hypercholesterolemia produced an additive effect, with a further decrease in both Na(+)-K(+)-ATPase activity and [3H]ouabain binding sites. Neither the activity of Mg+(+)-ATPase nor the binding affinity for [3H]ouabain was affected by either hypercholesterolemia or ischemia. These findings indicate that hypercholesterolemia may exaggerate certain aspects of functional deterioration arising during myocardial ischemia.

Animals↗

PubMed1996

Suppression of potassium currents by cyanide on the mouse motor nerve terminals.

NaCN at low concentrations markedly depressed the potassium currents in the motor nerve terminal of mouse triangularis sterni neuromuscular junction pretreated with potassium channel blockers 4-aminopyridine (4-AP), tetraethylammonium (TEA) or glucose-free medium. Neither azide nor dinitrophenol nor ouabain mimicked the effect of cyanide. This inhibitory effect of cyanide on nerve terminal spikes was correlated to its dramatic increase in spontaneous transmitter release under glucose-free condition. These results suggest that the effect of cyanide on the electrogenesis of nerve terminals is due to the direct suppression of ATP-sensitive K+ current since the effect was antagonized by ATP-sensitive K+ channels opener diazoxide and this may modulate the transmitter release.

2,4-Dinitrophenol↗

PubMed1996

Induction of HSP70 gene expression by modulation of Ca(+2) ion and cellular p53 protein by curcumin in colorectal carcinoma cells.

Curcumin (diferuloyl methane) is the major active yellow pigment of turmeric and curry. Studies in recent years have indicated that curcumin is a potent inhibitor of the initiation and promotion of chemical carcinogen-induced skin carcinogenesis in mice. When COLO205 colorectal carcinoma cells were treated with curcumin (60 microM), the appearance of apoptotic DNA ladders was delayed about 5 h, and G1 arrest was detected. Further analysis of the endonuclease activities in these cells revealed that the activity of Ca(+2)-dependent endonuclease in COLO205 cells was profoundly inhibited and that the extent of inhibition depended on the degree of calcium depletion. The reduction of p53 gene expression was accompanied by the induction of HSP70 gene expression in the curcumin-treated cells. These findings suggest that curcumin may induce the expression of the HSP70 gene through the initial depletion of intracellular Ca(+2), followed by the suppression of p53 gene function in the target cells.

3T3 Cells↗

PubMed1996

The effects of uranyl ions on neuromuscular transmission in the urinary bladder of the normal and streptozotocin-diabetic mouse.

The depressant effects of uranyl nitrate on the nerve-evoked muscle contraction of urinary bladder isolated from normal and streptozotocin-diabetic mice were compared. The non-cholinergic component of the evoked bladder contraction (in the presence of atropine) was specifically sensitive to the suppressive effect of uranyl nitrate. In contrast, the cholinergic component remaining after treatment with alpha, beta-methylene ATP was rather insensitive to uranyl nitrate. The contractile responses induced by KCl, acetylcholine and ATP were also not affected by uranyl nitrate, indicating a presynaptic site of action. High Ca2+ and calmodulin inhibitors (trifluoperazine, diltiazem and W7) antagonized the suppressive effects of uranyl ions. These results suggest that the depressant effects of uranyl nitrate is mediated by a reduction of prejunctional non-cholinergic transmitter release through the calcium-calmodulin pathway. In contrast to the normal bladder, the urinary bladder of streptozotocin-diabetic mice revealed not only weaker neurogenic contractile responses to electrical field stimulation, but also a profound reduction in the depressant effect of uranyl nitrate. These findings suggest that the Ca2+ regulation of non-cholinergic neurotransmission in mouse urinary bladder may be impaired in the diabetic state.

Animals↗

PubMed1996

Ruthenium red, a novel enhancer of K+ currents at mouse motor nerve terminals.

The effects of ruthenium red (RR) on transmitter release and pre-synaptic currents were studied in the mouse neuromuscular junction. The action of RR (10 microM) was shown not only in the complete suppression of nerve-evoked muscle contractions associated with the depression of endplate potential amplitude but also in the partial inhibition of the amplitude of miniature-endplate potentials. However, the other ruthenium compounds, ruthenium chloride and tris (2,2-bipyridyl) ruthenium chloride did not significantly affect the neuromuscular transmission. In pre-synaptic waveform studies, the fast K(+)-current [IK(f)] as well as the ca(2+)-activated K(+)-current [IK(ca)] was significantly enhanced by 10 microM RR. Furthermore, 10 microM RR antagonized the action of beta-bungarotoxin (a blocker of slow K(+)-channel [IK(s)] in enhancing pre-synaptic Ca2+ currents. In contrast, the typical Ca(2+)-channel blockers, omega-agatoxin (0.5 microM), Gd3+ (0.5 mM) and CD2+ (0.3 mM) all suppressed the IK(ca). Although RR (1-30 microM) inhibited the Ca(2+)-currents of the nerve terminals induced by the combined treatment with the K(+)-channel blockers, 3,4-diaminopyridine plus tetraethylammonium chloride in a concentration-dependent manner, it is considered that RR-enhanced K+ currents were responsible for, at least in part, the observed inhibition of the Ca(2+)-current which led to the blockade of transmitter release.

Animals↗

PubMed1996

Mutual interactions among ingredients of betel quid in inducing genotoxicity on Chinese hamster ovary cells.

The purpose of this study is to explore the mutual interactions among the chemical ingredients of betel quid including arecoline, sodium fluoride, catechin and glycyrrhizin in producing genotoxicity on Chinese hamster ovary (CHO) cells using the micronucleus method. Our results show that arecoline at a rather low concentration of 0.2-2 microM which could be in the oral cavity during betel quid chewing and NaF(0.8-2.4 mM) significant elevated the number of micronucleated cells in a concentration-dependent manner. In addition, significant prolongation of cell cycles was observed by treatment with arecoline (> or = 2.0 microM) or NaF (2.4 nM) in CHO cells. Both catechin and glycyrrhizin could antagonize not only the increased micronucleated cells induced by arecoline and NaF but also the prolonged cell cycle induced by arecoline in CHO cells. This find implies that the adjuvant ingredients, catechu and liquorice root extract provide not only a flavor but also an antagonist against the genotoxicity of arecoline and fluoride containing betel quid.

Animals↗

PubMed1996

Mechanism of cooling-induced relaxation in the isolated guinea-pig trachea.

In this study, we explored the possible mechanism of cooling-induced relaxation of the isolated guinea-pig trachea. A rapid cooling (-4 degrees C/min) from 37 +/- 0.5 degree C to 25 +/- 0.5 degree C induced a transient and small contraction followed by a sustained cooling-relaxation. This relaxation was not blocked by propranolol or tetrodotoxin. Various concentrations of four contractile agonists (histamine, carbachol, 5-HT and ryanodine) all enhanced cooling-relaxation in a concentration-dependent manner which correlated well with their increase in the developed muscular tension, suggesting an inherent counterbalance between cooling-relaxation and the bronchoconstriction. Treating with either indomethacin or nordihydroguaiaretic acid (NDGA) did not affect the contractile properties of histamine, carbachol and 5-HT except ryanodine, but reversed cooling-relaxation into sustained cooling-contraction. Indomethacin partially inhibited but NDGA abolished cooling-relaxation induced by ryanodine. Moreover, ryanodine, but not the other three contractile agonists, could antagonize indomethacin in inducing cooling-contractions by various agonists. From above findings, we can conclude that eicosanoids including prostaglandins particularly leukotrienes, which would be produced by the elevated Ca(2+)-release from the ryanodine sensitive Ca(2+)-store, play prominent roles in inducing cooling-relaxation.

Animals↗

PubMed1995

Functional assessment of Ca(2+)-current in the mouse motor nerve terminals.

The purpose of this study was to characterize voltage-gated Ca2+ channels on the mouse motor nerve terminals. Mouse diaphragm and triangularis sterni preparations were used for this study in order to assess the functional Ca2+ channels in the transmitter release. The results showed that omega-conotoxin MVIIC (CTx-MVIIC, 0.5-1 microM) but not omega-conotoxin GVIA (1 mM) markedly inhibits not only the nerve-evoked muscle contractions accompanied by a decrease in the amplitude of end plate potentials (epps) in the mouse phrenic-nerve diaphragm but also the Ca(2+)-waveforms in the nerve terminals of triangularis sterni. The inhibitory effects of CTx-MVIIC were considered to be specifically presynaptic rather than myogenic, since none of the electrical properties of muscle fibers including action potentials, resting membrane potentials and the miniature endplate potential, were affected. Moreover, Na(+)- and K(+)-waveforms of the nerve terminals were unaffected by CTx-MVIIC. At a saturating concentration of 3-5 mM, CTx-MVIIC exerted a maximal inhibitory effect by 38% of 3,4-diaminopyridine-prolonged epps area and inhibited only the slow component of Ca(2+)-current, respectively, and the remaining fast component could be inhibited by subsequent addition of cadmium chloride (Cd2+). All of these findings indicate that at least two components (a slow CTx-MVIIC sensitive component and a fast Cd2+ sensitive component) of the mouse motor nerve terminals would cooperate in the induction of the transmitter release from motor nerve endings.

Animals↗

PubMed1995

Relaxation of rat thoracic aorta induced by pyridine.

The pharmacological and toxicological activity of pyridine was determined in rat thoracic aorta. Pyridine inhibited norepinephrine (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by norepinephrine was also relaxed by the addition of pyridine and this relaxing effect was not affected by indomethacin (20 microM), NG-monomethyl-L-arginine acetate (50 microM) or methylene blue (50 microM). In high-K+ medium (80 mM), pyridine inhibited the Ca2+ concentration-dependent vasocontraction. Moreover, in Ca(2+)-free medium, the norepinephrine (3 microM)-induced phasic contraction was also suppressed by pyridine, while the caffeine (10 mM)-induced contraction remained unaffected. The cAMP and cGMP levels of rat aorta were not changed by pyridine. The 45Ca2+ influx elicited by either norepinephrine or high-K+ was inhibited by pyridine in a concentration-dependent manner. All of these findings indicated that pyridine relaxes rat thoracic aorta by virtue of its Ca2+ channel-blocking properties in vascular smooth muscle.

Animals↗

PubMed1995

Antagonism by paraquat of the relaxing effects of acetylcholine and A23187 in rat thoracic aorta.

Paraquat, a widely used herbicide, has been reported to be capable of producing superoxide. In the present paper, therefore, the possibility of paraquat inhibiting endothelium-dependent relaxation, mediated by the production of nitric oxide, was tested. The relaxing effects of acetylcholine and A23187, but not that of sodium nitroprusside, in the rat thoracic aorta were found to be inhibited by paraquat in a concentration-dependent manner. In contrast, paraquat was totally inactive with regard to the aortic contractions induced by either norepinephrine or prostaglandin F2 alpha. The inhibitory action of paraquat could be antagonized by superoxide dismutase but not by catalase and indomethacin. All of these findings indicate that superoxide anions produced by paraquat in the endothelium contribute to a decrease in the relaxation response to acetylcholine and A23187 by interfering with endothelium-derived nitric oxide.

Acetylcholine↗

PubMed1995

Enhancement of a slow potassium current component by uranyl nitrate and its relation to the antagonism on beta-bungarotoxin in the mouse motor nerve terminal.

Uranyl nitrate (UO2(NO3)2) has been shown to be capable of increasing transmitter release from the motor nerve accompanied by the potentiation of nerve evoked muscle contraction. In this paper, we have demonstrated that UO2(2+) induced an initial twitch depression followed by a later twitch potentiation in low (0.35 mM) Ca2+ medium. Although UO2(2+) has been identified as a K(+)-channel blocker, we have found it only partially blocked the fast K(+)-current (IK(f) as recorded in the perineurial sheath of the mouse triangularis sterni preparation. Increasing the concentration of UO2(2+) to a high concentration of 0.4 mM did not further inhibit IK(f) but markedly prolonged the duration of the outward current of the nerve terminals. From the time course of its appearance together with the specific inhibition by 4-aminopyridine, dendrotoxin and beta-bungarotoxin, which has been shown to be capable of blocking the K(+)-current of the motor nerve terminal, it was proposed that UO2(2+) prolonged the duration of the nerve terminal spikes by an enhancement of an IK(s)-like current, which was further characterized by its susceptibility to be enhanced by low K+, low Ca2+ and Cd2+ but attenuated by high K+ and high Ca2+. These cation effects not only supported UO2(2+)-induced IK(s) current but also excluded the possibility of an enhancement of Ca(2+)-activated K(+)-current induced by UO2(2+) plus TEA. The significance of this enhancement of IK(s) induced by UO2(2+) has been elucidated by the finding that dendrotoxin inhibited but tetraethylammonium potentiated not only UO2(2+)-induced IK(s) but also UO2(2+)-induced twitch depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

The in vivo effect of lipopolysaccharide on the spontaneous release of transmitter from motor nerve terminals.

1. The in vivo effect of E. coli lipopolysaccharide (LPS) on the spontaneous release of transmitter was studied in the isolated phrenic nerve-diaphragm preparation of the mouse. 2. The resting membrane potential was decreased and frequency of miniature endplate potentials (m.e.p.ps) was increased by treatment with LPS. 3. Pretreatment of diaphragms with ouabain markedly increased the frequency of m.e.p.ps in control group but not in the LPS group. 4. When mice were treated with polymyxin B (a LPS neutralizer), pentoxifylline (an inhibitor of tumor necrosis factor-alpha formation) and NG-nitro-L-arginine (an inhibitor of nitric oxide (NO) synthase) the effects of LPS were reversed. 5. These results suggest that LPS increases the spontaneous transmitter release through, at least in part, the pathways of tumour necrosis factor-alpha and NO followed by an inhibition of the Na(+)-pump activity in the endplate area.

Animals↗

PubMed1994

Potentiation by metal ions of ryanodine contracture of the mouse diaphragm.

The aim of this study was to elucidate the possible mechanism of the potentiating action of metal ions (Cu2+, Hg2+, Ag+ and SeO3(2-)) on the ryanodine-induced contracture of the mouse diaphragm. The ryanodine contracture in the quiescent muscle could be augmented by either electrical stimulation or pretreatment with high K+ of the diaphragm. Lowering the external Ca2+ concentration from 2.5 mM to 1 microM or the addition of 7 microM d-tubocurarine, which abolished the muscle excitability by blocking the receptors of acetylcholine, markedly attenuated the ryanodine contracture. Application of Cu2+, Hg2+, Ag+ and SeO3(2-) but not Ni2+ and Co2+, to quiescent muscle restored the ryanodine contracture. The potentiating effects of Hg2+, Ag+ and high K+ were dependent on the presence of external Ca2+ (2.5 mM) and intact transverse tubular systems but the effects of Cu2+ and SeO3(2-) were not. Treatment with 1 mM dithiothreitol 10 min after the application of metal ions and then subsequent addition of ryanodine abolished the potentiating effects of Hg2+ and Ag+ but not those of Cu2+ and SeO3(2-). Although ryanodine by itself had no effect on 45Ca2+ uptake by the mouse diaphragm, it significantly potentiated the increased 45Ca2+ uptake elicited by Cu2+ and Hg2+. Further elucidation of the interaction between metal ions and ryanodine on the outer sarcolemma showed that all of these metal ions, including the inactive Co2+ and Ni2+, not only decreased the membrane potential but also altered the membrane input resistance, effects which were not correlated with the potentiating effects of the metal ions on the ryanodine contracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Relaxation of rat thoracic aorta induced by 2,2',2''-tripyridine.

The pharmacological and toxicological activity of 2,2',2''-tripyridine was determined in rat thoracic aorta. 2,2',2''-Tripyridine inhibited norepinephrine (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by norepinephrine was also relaxed by the addition of 2,2',2''-tripyridine and this relaxing effect was not affected by indomethacin (20 microM) but partially antagonized by methylene blue (50 microM). In high-K+ medium (80 mM), 2,2',2''-tripyridine inhibited the Ca2+ concentration dependent vasocontraction. Moreover, in Ca(2+)-free medium, the phasic contraction induced by either norepinephrine (3 microM) or caffeine (10 mM) was also suppressed by 2,2',2''-tripyridine. Although the cAMP level of rat aorta was not changed by 2,2',2''-tripyridine, cGMP level was significantly increased by 2,2',2''-tripyridine. The increase in cGMP level caused by 2,2',2''-tripyridine was completely blocked by methylene blue (50 microM). The 45Ca2+ influx elicited by either norepinephrine or high-K+ was inhibited by 2,2',2''-tripyridine. All of these findings indicate that 2,2',2''-tripyridine relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.

Animals↗

PubMed1994

Studies on cytotoxic and genotoxic effects of cadmium nitrate and lead nitrate in Chinese hamster ovary cells.

Cadmium nitrate decreased the viability of Chinese hamster ovary (CHO) cells in a concentration-dependent manner; 50% inhibition (IC50) was achieved at 0.015 mM. In contrast, lead nitrate appeared to be less toxic. Neither cadmium nitrate nor lead nitrate significantly increased frequencies of binucleated CHO cells with micronuclei (MN). However, both cadmium nitrate and lead nitrate could augment sister chromatid exchanges (SCEs). Cadmium nitrate induced SCEs with a potency approximately equal to that of mitomycin C and more than 10 times higher than lead nitrate. Cadmium nitrate also increased chromosome aberrations (CAs), which included breaks, acentrics, interchanges, and dicentrics of chromosomes. In addition, cadmium nitrate induced a decrease in the mitotic index (MI), but lead nitrate increased it. In summary, it appears that both of these two heavy metal salts have cytogenetic toxicities with different degrees of effects on the cytotoxicity, MN, CAs, and SCEs in CHO cells. However, SCE was the most sensitive endpoint for indicating mutagenetic effects of cadmium and lead in the present study.

Animals↗

PubMed1994

Blockade by MPTP of the nicotinic acetylcholine receptor channels in embryonic Xenopus muscle cells.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on nicotinic acetylcholine (ACh) receptor channels were studied in cultured myocytes of 1-day-old Xenopus embryos. The amplitude and decay time of iontophoretic ACh-induced currents were reduced by MPTP in a concentration-dependent manner. The inhibitory action of MPTP was frequency-dependent, being enhanced by higher frequencies of stimulation at 7 and 30 Hz. Neither pargyline nor tranylcypromine affected the inhibitory effects of MPTP on ACh-induced currents. Single channel recordings showed that MPTP decreased the opening frequency, mean open time as well as the conductance of both low- and high-conductance ACh channels. These results suggest that the inhibitory actions of MPTP on ACh receptor channels in skeletal muscle may contribute to the depression of the nerve-evoked contraction of the mouse diaphragm as previously reported.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗