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Inhibition of 12-lipoxygenase reduces proliferation and induces apoptosis of hepatocellular carcinoma cells in vitro and in vivo

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Hepatobiliary & Pancreatic Diseases International 2012年第2期11卷 193-202页

作者： Xi-Ming Xu,Guang-Jin Yuan,Jun-Jian Deng,Hong-Ting Guo,Miao Xiang,Fang Yang,Wei Ge and Shi-You Chen Cancer Center, Renmin Hospital of Wuhan university, Wuhan 430060, China Cancer Center, the 82nd Hospital of the Chinese PLA, Huai’an 223001, China department of physiology, Medical College of Wuhan university, Wuhan 430071, China department of physiology & pharmacology, university of georgia, athens, ga 30602, usa [a] Cancer Center Renmin Hospital of Wuhan University Wuhan 430060 China [b] Cancer Center the 82nd Hospital of the Chinese PLA Huai'an 223001 China [c] department of physiology Medical College of Wuhan University Wuhan 430071 China [d] department of physiology & pharmacology University of Georgia Athens GA 30602 USA

BACKGROUND:12-lipoxygenase(12-LOX) has been reported to be an important gene in cancer cell proliferation and survival,and tumor ***,its role in hepatocellular carcinoma(HCC) cells remains ***:Expression of 12-LOX was assessed in a diethylnitrosamine-induced rat HCC model,and in SMMC-7721,HepG2 and L-02 cells using immunohistochemical staining and reverse transcriptase-polymerase chain reaction(RT-PCR).GST-π and Ki-67 were determined in vivo by immunohistochemical *** was evaluated by TUNEL *** viability and apoptosis were determined by MTT assay and flow cytometry,***-related proteins in SMMC-7721 and HepG2 cells were detected by Western ***:Immunohistochemical staining and RT-PCR showed that 12-LOX was over-expressed in rat HCC and two HCC cell lines,while the expression was inhibited by baicalein,a specific inhibitor of *** inhibited cell proliferation and induced apoptosis in rat HCC and both cell lines in a dose-and time-dependent *** in vivo study demonstrated that baicalein also reduced neoplastic ***,baicalein reduced Bcl-2 protein expression coupled with a slight increase of the expression of Bax and activation of ***,baicalein inhibited the activation of ERK-1/2(phosphorylated).Interestingly,the effects of baicalein were reversed by 12(S)-HETE,a metabolite of ***:Inhibition of 12-LOX leads to reduced numbers of HCC cells,partially caused by increased apoptosis.12-LOX may be a potential molecular target for HCC prevention and treatment.

关键词： hepatocellular carcinoma 12-lipoxygenase proliferation apoptosis

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Thermal Diversities of Two Na^+/H^+ Exchanges in Guinea Pig Red Cells

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Biomedical and Environmental Sciences 2001年第3期14卷 171-179页

作者： JI HONG-LONG 1department of Cellular Biology, university of georgia, athens, georgia 30602, usa department of Cellular Biology University of Georgia Athens Georgia 30602 USA. ji@physiology.uab.edu

Objective\ To test the effect of hypothermia on Na+/H+ exchange, activated by shrinkage and cytoplasmic acidosis. Method\ Amiloride-sensitive Na+ influx in guinea pig red cells was traced with isotope 22Na and intracellular Na+ concentration was measured by emission flame photometry. Result\ Amiloride-sensitive Na+ influx decreased linearly as a function of temperatures (about 37℃) in shrunken cells, but increased in acidified cells. The up-regulation of acid-induced Na+/H+ exchange by elevated temperature was enhanced by hypo-osmolarity. Less sensitivity of intracellular H+ site at 41℃ may be the mechanism for the inhibition of shrinkage-induced Na+/H+ exchange by elevated temperature. Heating-mediated explosive increase in the activity of acid-induced Na+/H+ exchange may be due to enhanced extracellular Na+ sensitivity and lower intracellular pH caused by acidic metabolites. Acid-induced Na+/H+ ewxchange contributes to cytoplasmic Na+ accumulation. Conclusion\ These two modes of Na+/H+ exchange with different response to elevated temperature may play different roles in the cellular pathogenesis of heatstroke.

关键词： Animals Cell Culture Techniques Erythrocytes Guinea Pigs Heat Stroke Hydrogen Ion Exchange Research Support, U.S. Gov't, Non-P.H.S. Sodium Temperature

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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou georgia Kouroupi Ilias Kazanis Laboratory of Developmental Biology Department of BiologyUniversity of PatrasPatrasGreece Laboratory of Cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur InstituteAthensGreece department of physiology School of MedicineUniversity of PatrasPatrasGreece

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal ***,we extended our investigation in two clinically-relevant ***,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian ***,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of *** found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian *** agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver ***,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin *** results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by ***,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells(iPSCs) neurotrophic factors Parkinson's disease substantia

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Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes

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Acta Pharmacologica Sinica 2004年第12期25卷 31-39页

作者： Yu FU2,3,4, Zi-tao ZHU2,5, Xing-zu ZHU2, Guo-zhang JIN2,6 2State KeyLaboratory of Drug Research,Shanghai Institute ofMateria Medica, Shanghai Institutes for BiologicalSciences, ChineseAcademy of Sciences, Graduate Schoolof the Chinese Academy of Sciences, Shanghai 201203, ChinaNow in department of pharmacology and Toxicology, Univer-sity of Texas Medical Branch, usa.Now in department of physiology & pharmacology, OregonHealth Sciences university, usa,5Now in department of physiology & pharmacology, OregonHealth Sciences university, usa, State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 201203 China

AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antago- nist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was re- corded in the nucleus accumbens (NAc) neurons of na?ve and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB-18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90 % of 6-OHDA-lesioned rats, while THPB-18 caused variable effects on the firing of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine, THPB-18 also possesses the “D1 agonistic-D2 antagonistic” dual action on the VTA-NAc DA system.4Now in department of pharmacology and Toxicology, Univer-sity of Texas Medical Branch, usa.5Now in department of physiology & pharmacology, OregonHealth Sciences university, usa,4Now in department of pharmacology and Toxicology, Univer-sity of Texas Medical Branch, usa.5Now in department of physiology & pharmacology, OregonHealth Sciences university, usa,5Now in department of physiology & pharmacology, OregonHealth Sciences university, usa,

关键词： berberine dopamine D1 receptors dopamine D2 receptors nucleus accumbens

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Effects of rat urotensin Ⅱ on coronary flow and myocardial eNOS protein expression in isolated rat heart

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Acta Pharmacologica Sinica 2004年第11期 60-65页

作者： Ling LI, Wen-jun YUAN, Ding-feng SUdepartment of pharmacology, department of physiology, Second Military Medical university, Shanghai 200433, China

AIM: To examine the effects of urotensin Ⅱ, a recently discovered endogenous peptide, on coronary flow (CF), cardiac function, and endothelial nitric oxide synthase (eNOS) expression in isolated rat hearts. METHODS: Heart was isolated and perfused retrogradely via the aorta in Langendorff mode. Rat urotensin Ⅱ was administered in the perfusion solution. The eNOS content in myocardium was determined by Western blot. RESULTS: Rat urotensin Ⅱ had no effect on the heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, or ±dp/dtmax. While rat urotensin Ⅱ dose-dependently increased CF. CF was increased by 11.43 %, 6.67 %, 6.62 %, 6.56 %, 6.36 %, and 5.86 % respectively in a time-dependent manner at 5, 10, 15, 20, 25, and 30 min after injection of rat urotensin II 6.66×10-2μg. The maximal effect on CF was found at 5 min following urotensin II administration. NG-nitro-L-arginine methyl ester (L-NAME) did not prevent the increased CF in response to urotensin II. Rat uroten

关键词： urotensin Ⅱ nitric oxide synthase nitric oxide heart function tests coronary circulation rats

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Distribution of ^3H—nicotine in Rat Tissues Under the Influence of Simulated Microgravity

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Biomedical and Environmental Sciences 1999年第2期12卷 103-109页

作者： PARIMAL CHOWDHURY MICHAEL E. SOULSBY AND JAMES N. PASLEY (department of physiology and Biophysics, university of Arkansas for Medical Scienses, Little Rock, Arkansas 72205, usa) Institute of Occupational Medicine Chinese Academy of Preventive Medicine 29 Nan Wei Road Beijing 100050 China

Rat tail suspension offers a useful model to reproduce physiologic responses to *** present study was conducted in the head-down-tilt(HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30°for two weeks on a 12/12 light/dark cycle. During this period,body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected IV withe a solution contaming 4 microuries of micotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain,blood,trachea,salivary gland,lung,heart,esophagus,spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determinded and ealeulated as percent of total injected radioactivity. Final body weights of suspended ammals were significantly (P gastrointestinal tissues. compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues:esphyagus (25 %), aorta (25%). fundus (25%), trachea (22%), adrenals (18%), spleen (17 %), and pancreas (12 %). The decreased retention of mcotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differnces in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.

关键词： Gravitation Animals Male Nicotine Rats Rats, Sprague-Dawley Research Support, Non-U.S. Gov't Tissue Distribution Tritium Weightlessness Simulation

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Estrogen influences the differentiation, maturation and function of dendritic cells in rats with experimental autoimmune encephalomyelitis

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Acta Pharmacologica Sinica 2004年第4期25卷 110-115页

作者： Qing-hong ZHANG2, Yu-zhen HU, Jun CAO3, Yan-qing ZHONG,Yu-feng ZHAO, Qi-bing MEI4 department of physiology, department ofOrthodontics, 3 4department of pharmacology, The Fourth Military Medical university, Xi’an 710032, China department of physiology The Fourth Military Medical University Xi'an 710032 China

AIM: To examine if estrogen can affect the immune response at the dendritic cells (DCs) level in rats with experi- mental autoimmune encephalomyelitis (EAE). METHODS: Lewis rats were immunized with inoculum containing MBP68-86. DCs were derived from spleen monocytes of EAE rats with IL-4 and GM-CSF in presence of 17β- estradiol (E2). Nitric oxide (NO) was detected by Griess reagent. The surface markers and cytokines production of DCs were shown by flow cytometry. DCs were cocultured with MBP-specific T cells, [3H]-TdR incoportation was used to reveal the antigen presentability, the supernatant of the coculture were collected to examine the cytokines secretion by ELISA. RESULTS: E2 activated DCs by accelerating the maturation process characterized by upregulation of MHC II and costimulating molecule B7-1, B7-2, drastic high expression of CD40. IFN-γ–produc- ing DCs were also elevated without any alteration of IL-10. Estradiol-treated DCs (E2-DCs) secreted more NO in the culture supernatant. By contrast, E2-DCs showed decreased antigen presentation ability with reduced secretion of IFN-γ but no alteration of IL-10 in the coculture with T cells. CONCLUSION: Estrogen can affect the differentiation, maturation and function of DCs from EAE rats, which may be attributed to its protection against EAE and the remission of multiple sclerosis patients in pregnancy.

关键词： multiple sclerosis experimental autoimmune encephalomyelitis dendritic cells estrogens nitric oxide

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Problem-based learning in pharmacology:a survey of department heads in Taiwan, China

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Acta Pharmacologica Sinica 2004年第9期 137-139页

作者： Ying-tung LAUdepartment of physiology and pharmacology School of Medicine, Chang Cung university, Taoyuan, Taiwan, China

Problem-based learning (PEL) requires active student participation and the use of clinical cases as a trigger to learn within a given area. It has gained much attention as a pedagogic alternative in the course of reform in medical education due to information overload. From discipline-based consideration, it is interesting to understand the views of department heads of pharmacology about implementing PBL for their medical students. According to a

关键词： problem-based learning pharmacology medical education

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Changes in Autoantibodies against β1-Adrenoceptor and M2-Muscarinic Receptor during Development of Renovascular Hypertension in Rats

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Acta Biochimica et Biophysica Sinica 2004年第12期36卷 793-797页

作者： Jian-Ming ZHI*, Rong-Fang CHEN1, Heng WU2, Hui-Rong LIU2, and Rong-Rui ZHAO2 department of physiology, Shanghai Second Medical university, Shanghai 200025, China 1department of Toxicology, Second Military Medical university, Shanghai 200433, China 2 department of physiology, Shanxi Medical university, Taiyuan 030001, China department of physiology Shanghai Second Medical UniversityShanghai 200025 China department of Toxicology Second Military Medical UniversityShanghai 200433 China department of physiology Shanxi Medical UniversityTaiyuan 030001 China

In an experimental rat’s renovascular hypertension model, we studied the genesis of anti- cardiac β1-adrenoceptor and M2-muscarinic receptor autoantibodies in relation to the changes in immunological function during the development of renal hypertension. The biological activities of these autoantibodies were also examined. It was shown that after two weeks of operation both the frequency of occurrence and the titre of autoantibodies to cardiac β1-adrenoceptor and M2-muscarinic receptor were significantly increased as compared with the control of pre-treatment. The increased autoantibodies lasted for several weeks and then automatically decreased gradually to the pre-clipping level at 10 weeks. Meanwhile the ratio of CD4 /CD8 + + was also undergone an initial increase followed by gradual recovery and correlated well with the changes in antibody titre. The biological effects of these autoantibodies displayed an “agonistic-like” activities on the beating frequency of cultured neonatal cardiomyocyte. It is suggested that autoimmune mechanisms are involved in the pathogenesis of renal hypertension and the cardiac receptor autoantibodies might be one of the mechanisms leading to cardiac dysfunction.

关键词： autoantibody renal hypertension cardiac receptor immunology

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Effects of 13-methyltetradecanoic acid on injury of cultured BMECs in vitro induced by oxygen paradox

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中国病理生理杂志 2010年第A10期26卷 2042-2043页

作者： YU Juan1,WENG Sheng-mei2,HU Chun-lan1(1department of physiology and Pathophysiology 2department of pharmacology,Fujian Medical university,Fuzhou 350004,China)

AIM:To observe the protective effects of 13-methyltetradecanoic acid(13-MTD)on the injury of cultured brain microvascular endothelial cells(BMECs)induced by oxygen paradox. METHODS:Two screen filtration methods and en... 详细信息

关键词： cultured paradox protective neonatal digestion cortex microvascular filtration screen staining

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