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Biomedical subjects

A Y Sun

Publications and source records attributed to A Y Sun.

At least 37 records · Page 2Linked to original sources
PubMed1997

Enhanced (Na+K)-ATPase activity and expression in mouse brain after chronic ethanol administration.

It is the general hypothesis that the primary mode of action of ethanol is the alteration of membrane structure and function including the conformation of receptors and ion channels essential for neurotransmission and signal transduction. However, the issue of whether ethanol affects (Na+K)-ATPase under physiological conditions remains unsettled. In this study, adult mice were treated with a daily dose of 5 g/kg of ethanol for 28 days. The RNA was isolated from brain and the (Na+K)-ATPase mRNA level was determined using Northern blot analysis. We have found an increased expression of (Na+K)-ATPase alpha-subunit in the chronically treated alcohol group as compared with that of controls. This result was further substantiated by increased protein phosphorylation as well as increased specific activity of this enzyme in the synaptosomal plasma membrane after chronic ethanol administration. Thus we have demonstrated that ethanol may directly affect (Na+K)-ATPase in vivo, leading to the increased synthesis of this enzyme through adaptive mechanisms.

Alcoholism↗
PubMed1997

gon-2, a gene required for gonadogenesis in Caenorhabditis elegans.

The gonad of the Caenorhabditis elegans hermaphrodite is generated by the postembryonic divisions of two somatic precursors, Z1 and Z4, and two germline precursors, Z2 and Z3. These cells begin division midway through the first larval stage. By the end of the fourth larval stage, Z1 and Z4 produce 143 descendants, while Z2 and Z3 give rise to approximately 1000 descendants. The divisions of Z2 and Z3 are dependent on signals produced by Z1 and Z4, but not vice versa. We have characterized the properties of five loss-of-function alleles of a newly described gene, which we call gon-2. In gon-2 mutants, gonadogenesis is severely impaired; in some animals, none of the gonad progenitors undergo any postembryonic divisions. Mutations in gon-2 have a partial maternal effect: either maternal or zygotic expression is sufficient to prevent the severe gonadogenesis defects. By cell lineage analysis, we found that the priman, defect in gon-2 mutants is a delay (sometimes a complete block) in the onset and continuation of gonadal divisions. The results of upshift experiments using a temperature-sensitive allele suggest that zygotic expression of gon-2 begins early in embryogenesis, before the birth of Z1 and Z4. The results of downshift experiments suggest that Z1 and Z4 can generate the full complement of gonadal tissues even when gon-2 function is inhibited until the end of the second larval stage. Thus, gon-2 activity is probably not required for the specification of gonadal cell fates, but appears to be generally required for gonadal cell divisions.

Animals↗
PubMed1996

Chronic ethanol on mRNA levels of IP3R1, IP3 3-kinase and mGluR1 in mouse Purkinje neurons.

Chronic ethanol exposure is known to alter the polyphosphoinositide (poly-PI) signaling pathway, although the exact sight of regulation is not well understood. In this study, C57B1/6J mice were given a control or an ethanol (6 g kg-1 body wt) liquid diet by gastric intubation daily for 4 weeks. Examination of levels of mRNA for type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), inositol 1,4,5-trisphosphate 3-kinase (IP3K) and metabotropic glutamate receptor 1 (mGluR1) in cerebellar Purkinje neurons by in situ hybridization revealed significant decreases in cellular levels of mRNA encoding both IP3R1 and mGluR1 in the ethanol-treated group compared with controls, but levels of IP3K mRNA were not altered. These results suggest that chronic ethanol consumption selectively alters cellular mRNA in the poly-PI signaling pathway. The decrease in mRNA levels of mGluR1 and IP3R1 may be an important underlying mechanism towards explaining the alcohol-induced degenerative changes in the cerebellar Purkinje neurons.

Alcoholism↗
PubMed1996

Enhanced lipid peroxidation by extracellular ATP in PC12 cells.

Recently we have demonstrated that extracellular ATP acts as an excitatory neurotransmitter and enhances cell death in the presence of ferrous ions. By using a newly developed cis-parinaric acid fluorescence technique, we demonstrated that ATP, in a dose dependent manner, enhanced the increased membrane lipid peroxidation in PC12 cells when cells were incubated with micromolar FeCl2/DTP. P2 purinoceptor agonists, alpha,beta-methylene ATP and 2-methylthio-ATP, induced PC12 cell lipid peroxidation, but to a lesser extent than ATP. ATP-induced Ca(2+) influx via P2 purinoceptor activation significantly increased the intracellular Ca(2+)concentration, which may have triggered a free radical generating cascade(s), and led to membrane lipid peroxidation and cell death. Since oxidative stress has been implicated in certain neurodegenerative diseases such as aging, extracellular ATP may contribute to neuronal cell death by an oxidative mechanism involving lipid peroxidation.

Adenosine Triphosphate↗
PubMed1996

Effects of m-nisoldipine on aortic calcium accumulation in rats with vascular calcium overload.

AIM: To study the effects of a novel calcium channel blocker, m-nisoldipine, on vascular calcium overload (VCO) at both tissue and cellular levels. METHODS: VCO was induced in Wistar rats by treatment with colecalciferol (Col, 400,000 IU.kg-1, p.o.) and an aqueous mixture of ethanol and polyethyleneglycol-400 for 3 d. The tissue and subcellular calcium contents of aorta were determined by atomic absorption spectrometer and electron probe microanalysis, respectively. RESULTS: Chronic treatment with m-nisoldipine (m-Nis, 1-15 mg.kg-1, p.o., bid) only had mild inhibition on the elevation of total calcium in aorta, and the dose-response relationship of m-Nis displayed a bell shape, with inhibition ratio of 24% only for m-Nis 2.5 mg.kg-1. The effect of verapamil (12.5 mg.kg-1, p.o., bid) was a little better than that of m-Nis. The intracellular VCO in medial smooth muscle cells of aorta were remarkably inhibited by m-Nis (2.5 mg.kg-1), with inhibition ratios of 72% for cytoplasm and 76% for mitochondrion. The calcium accumulation in nucleus was reduced to a lesser degree than those in cytoplasm and mitochondrion. CONCLUSION: As for aorta in VCO rats, m-Nis mainly had conspicuous inhibition on intracellular VCO in medial smooth muscle cells, particularly in cytoplasm and mitochondrion, but with little effect on extracellular calcium deposition at tissue level.

Animals↗
PubMed1995

Restraint stress changes heart sensitivity to arrhythmogenic drugs.

AIM: To study the effects of acute restraint stress on ventricular electric stability (VES) and its mechanisms of action. METHODS: VES was evaluated both in vivo and in vitro by the changes of arrhythmogenic responses to icv or ip aconitine in rats and iv BaCl2 or adrenaline in rabbits following restraint stress for different durations. Pretreatments and the assay of heart-specific enzymes were made. RESULTS: The heart sensitivity to these drugs was promoted after stress for 2 h, but obtunded after stress for 8 h (the latency of ventricular arrhythmia to icv aconitine was shortened from 4.1 +/- 0.9 min in control rats to 2.9 +/- 0.9 min after stress for 2 h, P < 0.05; but prolonged to 9.3 +/- 3.8 min after stress for 8 h, P < 0.05). In Langendorff heart, the changes of VES induced by stress were similar to those in vivo, but to lesser degree. Pretreatment with adrenalectomy inhibited the descending phase of VES, while pretreatment with both aminophylline and vagotomy remarkably depressed the ascending phase at 8 h. In addition, the serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase and their isozymes, LDH1 and CK-MB, were elevated at 2 h, and rose continuously at 8 h. CONCLUSION: Acute restraint stress causes biphasic changes of VES. The initial decrease of VES was related to adrenal catecholamine release, whereas the following increase of VES was ascribed to adaptive decrease of cAMP and vagal activation. The changes of VES did not always parallel the injury of heart.

Aconitine↗
PubMed1994

Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons.

In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent, alpha-phenyl-N-tert- butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synthase may also play a role in KA insult.

Allopurinol↗
PubMed1994

Effects of extracellular ATP on Fe(2+)-induced cytotoxicity in PC-12 cells.

Extracellular ATP is known to cause a variety of changes, including the alteration of ion fluxes, cell growth, and other physiological activities. Recently, it has been suggested that ATP acts as an excitatory synaptic transmitter, which may produce a Ca2+ influx via the activation of a P2y purinoceptor. Rat pheochromocytoma (PC-12) cells are known to resemble rat sensory neurons and to possess a P2y purinoceptor. In this study, we demonstrated that extracellular ATP dose-dependently increased PC-12 cell death in the presence of ferrous ions. Voltage-sensitive calcium channel blockers and calpain and xanthine oxidase inhibitors were found to be effective at protecting PC-12 cells from Fe2+/ATP-induced lipid peroxidation and cell death. These results suggest that xanthine oxidase activation induced by calpains and subsequent free radical formation may be responsible for Fe2+/ATP-induced neuronal cell death.

Adenosine Triphosphatases↗
PubMed1994

Cardiovascular responses to intracerebroventricular injection of GABA in renovascular hypertensive rats.

Effects of central GABAergic stimulation on cardiovascular function were evaluated in 2-kidney, 1-clip (2K1C) renovascular hypertensive rats (RVHR). Intracerebroventricular injection (icv) of GABA (100 and 200 micrograms) reduced blood pressure (BP) to a greater degree in RVHR as compared with sham-operated controls, and the greatest response was seen in RVHR 4 wk after operation (4 wk-RVHR). In addition, a decreased sensitivity of baroreflex was observed in 4 wk-RVHR, and was improved by icv GABA. Pretreatment with icv captopril (200 micrograms) only reduced BP moderately in 4 wk-RVHR, but attenuated remarkably the depressor effect of GABA. On the contrary, pretreatment with ip captopril was less effective in attenuating the depressor effect of GABA. Our results indicated that RVHR was deficient in central GABAergic inhibition on BP control, for GABAergic stimulation reduced BP to a greater degree and improves the decreased sensitivity of baroreflex in RVHR; the depressor effect of GABA is mediated, at least in part, by inhibiting brain angiotensin system.

Animals↗
PubMed1993

Effects of ethanol on brain monoamine content of spontaneously hypertensive rats (SHR).

Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE), epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in different brain regions were determined. Results indicated a 3-fold increase in NE level in brain stem and hypothalamus and more than 2-fold increase in DA in corpus striatum in alcohol-treated rats as compared to controls. There was a significant increase in the level of DA in the corpus striatum but the levels in cerebral cortex, brain stem and hippocampus were decreased instead. Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and cerebellum of alcohol-treated brain as compared to untreated controls. These results indicate alterations of the biogenic amine contents in different regions of the SHR brain after chronic ethanol ingestion. Since stimulated release of biogenic amines in the SHR brain has been implicated in the regulation of blood pressure, changes due to ethanol ingestion may be a risk factor in hypertensive patients.

Animals↗
PubMed1993

Manganese exposure to PC-12 cells alters triacylglycerol metabolism and promotes neurite outgrowth.

Exposure of PC-12 cells to MnCl2 (10-100 microM for 1 to 3 days) resulted in both morphological and metabolic changes as indicated by promotion of neurite outgrowth and an increased incorporation of labeled fatty acids (14:0, 18:1 and 20:4) into triacylglycerols (TG). Cells prelabeled with [14C]arachidonic acid (AA) showed a time-dependent decrease in labeled TG, and the rate of decline was inhibited by Mn (100 microM). In the pulse-chase type of study, the decrease in the proportion of labeled TG as well as labeled phosphatidylcholine (PC) was marked by an increase in labeled phosphatidylinositol and phosphatidylethanolamine. These results support previous notion that TG plays an important role in channeling the fatty acid nutrients for biosynthesis of membrane phospholipids. Thus, the Mn-induced inhibition of the ability to transfer TG fatty acids to other lipids in PC-12 cells may be an underlying cause for the observed morphological changes.

Animals↗
PubMed1993

Effects of chronic ethanol administration on poly-phosphoinositide metabolism in the mouse brain: variance with age.

Using a procedure in which poly-phosphoinositides (poly-PI) in C57Bl mouse brain were labeled with [32P]Pi or [32P]ATP, the effects of chronic ethanol administration and age on metabolism of these anionic phospholipids were examined. Within 4 h after intracerebral injection, both labeled precursors were effectively incorporated into membrane phospholipids with high proportions of labeling among phosphatidylcholine, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate. With few exceptions, the phospholipid labeling patterns in different brain regions, e.g. cortex, hippocampus and hypothalamus, were similar. However, when the brain homogenate was subjected to differential and sucrose-Ficoll gradient centrifugation, different phospholipid labeling patterns were observed in the subcellular membrane fractions. Young adult mice given an ethanol (5% w/v) liquid diet for 2 months showed an increase in the levels of labeled phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylserine in the cortex and hippocampus as compared to the pair-fed controls, but these changes were not observed in the hypothalamus. In another study, 12- and 26-month-old mice were administered either an ethanol (8 g/kg in two doses daily) or a control diet by gavage for 3 weeks. The 12-month-old group given the ethanol diet showed an increase in labeled poly-PI which was found largely in the synaptosomal fraction. Surprisingly, the 26-month-old mice given the same ethanol paradigm showed a decrease in labeled poly-PI. Consistent with our previous observations, the 26-month-old mice showed a higher proportion of labeled poly-PI in the synaptosomal fraction as compared to the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Antifibrillatory effect of tetrahydroberberine.

Electric stimulation and drug-induced ventricular fibrillation (VF), monophasic action potentials (MAP), and triggered activity were studied before and after administration of tetrahydroberberine (THB) in rabbits, rats or guinea pigs. At doses of 5, 10, and 20 mg.kg-1, i.v. THB increased the ventricular fibrillation threshold, and the BaCl2-induced VF was also prevented or terminated by THB in rabbits. Centrogenic VF induced by icv aconitine in rats was inhibited by pretreatment with THB in a dose-dependent manner, whereas VF induced by iv ouabain in guinea pig was inhibited to a lesser degree. For MAP, the duration at 90% repolarization (MAPD90) was prolonged remarkably, whereas the MAPD20, the MAP amplitude, and the maximal velocity of phase 0 were shortened or decreased slightly. The amplitudes of early afterdepolarization produced by cesium chloride (CsCl) were attenuated, while the cumulative threshold doses of CsCl for sustained ventricular tachycardia were elevated by THB. These results indicated that THB had an potent antifibrillatory effect, which might be attributed to its blockade of potassium, calcium, and sodium currents.

Aconitine↗
PubMed1992

The biochemical mechanisms of the excitotoxicity of kainic acid. Free radical formation.

Kainic acid (KA) is a known potent neuroexcitotoxin, although the biochemical mechanism producing its underlying neurotoxic effect is not quite clear. Histopathological examination of gerbil brains 24 h after systemic injection of KA revealed severe neuronal lesions in different regions of the brain, especially the cerebellar and hippocampal areas. We have detected free radical formation in the brain 1 h after KA administration by using an in vivo spin trapping technique. We have also observed increased lipid peroxidation in the brain after KA-treatment by analyzing thiobarbituric acid reactive substances and conjugated diene formation. Diminished brain specific (Na+, K+)-ATPase activity was also found 2 h after KA injection and persisted to 24 h. It is possible that the free radical reaction is a primary cause of neuronal degeneration after KA administration.

Animals↗