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Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptorinduced cardiomyocyte hypertrophy

Acta Pharmacologica Sinica 2006年第7期27卷 895-900页

作者： Da-li LUO~(2,3.5) Jian GAO~2 Xiao-mei LAN~3.Gang WANG~4 Sheng WEI~4 Rui-ping XIAO~4 Qi-de HAN~3. Department of Pharmacology,School of Chemical Biology & Pharmaceutical sciences,Capital university of Medical sciences,{3. 100069,china 3.Institute of cardiovascular science at health science center,peking university beijing 100083.china 4 Institute of Molecular Medicine and College of Life science,peking university,{3. 100871,china Department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing 100069 China Institute of cardiovascular science at health science center Peking University Beijing 100083 China Institute of Molecular Medicine and College of Life science Peking University Beijing 100871 China

Aim:Intracellular Ca2+plays pivotal roles in diverse cellular functions,includinggene transcription that underlies cardiac remodeling during stress ***,the role of inositol 1,4,5-trisphosphate receptors（IP3.s）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3.smay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3.s was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3.M）,a membrane-permeant ester of IP3.to activate IP3.s directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3.M(10μmol·L-1)mimicked theeffects of phenylephrine,a selective agonist of α1AR,in increments in local Ca2+spark release（especially in the perinuclear area）and global Ca2+*** importantly,IP3. inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3.M-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3.]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3. signaling to α1AR-stimulatedgene expression and cardiomyocyte hypertrophy.

关键词： inositol 1,4,5-trisphosphate receptors Ca2+sparks α1 adrenergic stimulation cardiac hypertrophy

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Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide

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Acta Pharmacologica Sinica 2004年第6期25卷 131-136页

作者： Qi-zhen CAO, Zhi-bin LIN1 Department of Pharmacology, health science center, {3. university, beijing 100083, china Department of Pharmacology Health Science Center Peking University

AIM: To investigate the antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide (GLPP). METHODS: Antitumor effect of GLPP was observed in tumor-bearing mice in vivo. At the same time, the effects of GLPP on proliferation of tumor cells and human umbilical cord vascular endothelial cell (HUVEC) were detected by MTTassay in vitro. Subsequently, spleen lymphocytes proliferation of nude mice was stimulated by LPS or ConA. To investigate the anti-angiogenic effect of GLPP, GLPP 80 μg per disc and GLPP-treated serum 10 μL per disc were added to the chick chorioallantoic membrane (CAM) respectively in vivo. RESULTS: GLPP 50, 100, and 200 mg/kg inhibited growth of Sarcoma 180 in BALB/c mice markedly by 3..2 %, 45.2 %, and 61.9 %, respectively. GLPP which was directly added to the cultured medium did not inhibit PG cell proliferation in vitro; but GLPP-treated serum 50, 100, 200 mg/kg potently inhibited PG cell proliferation by 22.5 %, 26.8 %, and 3..3.%, respectively; and reduced the xenograft (human lung carcinoma cell PG) in BALB/c nude mice greatly in vivo by 55.5 %, 46.0 %, and 46.8 %, respectively. Lymphocytes proliferation of nude mice could be stimulated by LPS 5 mg/Lbut not by ConA 2.5 mg/L, indicating that GLPP could not promote the T lymphocyte proliferation and neutral red phagocytosis of peritoneal macrophages of nude mice. The CAM assay showed that GLPP and GLPP-treated serum had anti-angiogenic effect. GLPP (1, 10, and 100 mg/L) inhibited HUVEC proliferation in vitro with the inhibitory rate of 9.4 %, 15.6 %, and 40.4 %, respectively. CONCLUSION: GLPP has antitumor and anti- angiogenic activity. The anti-angiogenesis of GLPP may be a new mechanism underlying its anti-tumor effects.

关键词： Ganoderma lucidum polysaccharides sarcoma 180 adenocarcinoma lung neoplasms lympho- cyte proliferation peritoneal macrophages angiogenesis nude mice

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Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3.plus nicotine in rats

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Acta Pharmacologica Sinica 2006年第3期27卷 299-306页

作者： Sheng-ying WU~(2,6) Chun-shui PAN~3.Bin GENG~3.Jing ZHAO~3.Fang YU~3.Yong-zheng PANG~3.Chao-shu TANG~4 Yong-fen QI~(3.4,5) ~2Institute of cardiovascular Disease,peking university First Hospital.{3. 10003. ~3.epartment of Physiology and Pathophysiology,peking university health science center,{3. 100083.china,~4Key Laboratory of Molecular cardiovascular science,Ministry of Education,{3. 100083.china 2Institute of cardiovascular Disease Peking University First Hospital Beijing 100034 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 4Key Laboratory of Molecular cardiovascular science Ministry of Education Beijing 100083 China 4Key Laboratory of Molecular cardiovascular science Ministry of Education Beijing 100083 China

Aim:To investigate the role of the endogenous cystathionine γ-synthase(CSE)/hydrogen sulfide(H2S)pathway in vascular calcification in ***:A ratvascular calcification model was established by administration of vitamin D3.plusnicotine(VDN).The amount of CSE and osteopontin(OPN)mRNA was deter-mined by using semi-quantitative reverse-transcription polymerase chain *** calcium content,45Ca2+accumulation and alkaline phosphatase(ALP)activitywere measured.H,S production and CSE activity were ***:yonKossa staining produced strong positive black/brown staining in areas amongthe elastic fibers of the medial layer in the calcified *** calcium content,45Ca2+accumulation and ALP activity in calcified arteries increased by 6.77-,1.42-,and 1.87-fold,respectively,compared with *** expression of the OPNgene was upregulated(P3..8%,40.75% and 63.5% lowerin the low-dosage NariS group than in the VDN group,respectively(P3.9%,3..8 % and 46.2% lower in the aorta in the high-dosage NariS group than in theVDN group,respectively(P<0.01).The expression of the OPN gene ***:The production of H,S,and CSE activity were de-creased and CSE gene expression was downregulated in rats with vascularcalcification.H2S can ameliorate vascular calcification,suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.

关键词： hydrogen sulfide cystathionine-lyase vascular calcification mRNA

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Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

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Acta Pharmacologica Sinica 2004年第03期25卷 87-92页

作者： Lin CHANG2,3.Jian-xin XU4,Jing ZHAO5,Yong-zheng PANG2,3.Chao-shu TANG2,3.Yong-fen QI5,6 2Institute of cardiovascular Diseases,the FirstHospital,peking university,{3. 10003. 3.nstitute of cardiovascular Diseases,peking university,{3. 100083 4Instituteof Biophysics,Chinese Academy of sciences,{3. 100101 5Department of Physiology,health science {13.,peking university,{3. 100083.china Institute of cardiovascular Diseases the First Hospital Peking University Institute of cardiovascular Diseases Peking University Institute of Biophysics Chinese Academy of Sciences Beijing 100101 Department of Physiology Health Science Center Pe

AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS) — hydrogen peroxide (H2O2) and superoxide anion (O2ˉ· )were measured with luminol or lucigenin chemiluminescences method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocystenie, was increased (P0.05 vs control). In this study, the superoxide anion in VSMC was not detectable by chemiluminent method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition, co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

关键词： homocysteine taurine vascular smooth muscle mitochondria reactive oxygen species

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Petrogenesis of Songshugou dunite body in the Qinling orogenic belt, Central china: Constraints from geochemistry and melt inclusions

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science china Earth sciences 2005年第8期48卷 1146-1157页

作者： SU Li1,2, SONG Shuguang3.& ZHOU Dingwu1 1. Key Laboratory of Continental Dynamics of the Ministry of Education, Department of Geology, Northwestern university, Xi’an 710069, china 2. The Geological Lab center, china university of Geosciences (beijing), beijing 100083, china 3. Key Laboratory of Orogenic Belts of the Ministry of Education, Department of Geology, peking university, beijing 100871, china 1. Key Laboratory of Continental Dynamics of the Ministry of Education Department of Geology Northwestern University 710069 Xi’an China 2. The Geological Lab center China University of Geosciences 100083 (Beijing)Beijing China 3. Key Laboratory of Orogenic Belts of the Ministry of Education Department of Geology Peking University 100871 Beijing China

The Songshugou dunite body, which occupies an area of about 20 km2, is the largest ultramafic massif in the eastern Qinling orogenic belt, Central china. The major compo-nent of this body is dunitic rocks including mylonitic dunite and coarse-grained dunite; they oc-cupy about 95 vol% of the total body. Petrography, mineral composition, major and trace ele-ments and primitive melt inclusions have been investigated in this paper; all revealed that this dunite body is the product of melt-rock interaction by porous percolation flow. In comparison with dunite sills or veins in harzburgite from the basal part of Oman ophiolite, this dunite body is characterized by lower contents of Al2O3. CaO and HREE but higher content of highly incom-patible elements and Zr and Hf. The LREE enriched patterns and primitive mantle normalized spidergrams of trace elements are also different from the Oman dunite. Combining with melt in-clusions observed in olivines, we conclude that this dunite body is the product of large- scale porous percolation flow of high-MgO melts within depleted mantle peridotites. The high-MgO magma, in essence, was most probably produced at the hot head of an upwelling mantle plume. The occurrence of the Songshugou dunite body is closely associated with the activity of mantle super-plume in Neo-Proterozoic era in the Yangtze Craton.

关键词： Songshugou dunite body, geochemistry, melt inclusion, mantle plume, Qinling orogenic belt.

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p3. MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

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Acta Pharmacologica Sinica 2004年第3期25卷 12-16页

作者： Rui-mao ZHENG,Chang-jiang ZOU,Shi-gong ZHU2 Department of Physiology and Pathophysiology,health science center,{3. university,beijing 100083.china Department of Physiology and Pathophysiology Health Science Center Peking University Beijing 100083 China

AIM: To investigate the roles of p3. mitogen-activated protein kinase (p3. MAPK) in the cardiovascular and behavioral responses induced by intracerebral ventricular injection (icv) of interleukin-1β (IL-1β) or footshock. METHODS: We examined the effects of p3. MAPK on mean artery blood pressure (mABP), heart rate (HR), and motor activity (MA) during central administration of IL-1β, or footshock after icv SB203.80 (a specific inhibitor of the p3. MAPK) with cardiovascular and Behavior Telemetry System in conscious SD rats. RESULTS: (1) IL-1β (icv) or footshock remarkably rise the mABP, and the maximal changes are (7.8±1.8) and (12.3.3.5) mmHg, respectively, which was abrogated by the pretreatment with p3. inhibitor SB203.80 intracerebroventricularly. (2) Compared with icv saline group, the motor activity was significantly decreased in SB203.80 group with maximal changes (-7.6±1.1) counts/min after footshock. CONCLUSION: p3. MAPK plays an important role in the pres- sor response induced by central administration of IL-1β or footshock and change of motor activity after footshock in conscious rats.

关键词： mitogen-activated protein kinase p3. interleukin-1 blood pressure motor activity

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Response synchronization: New progress in brain-visual information processing

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Chinese science Bulletin 1999年第16期44卷 1447-1458页

作者： ZHAO Songnian, XIONG Xiaoyun, YAO Guozheng and GUO Aike1. State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry , Institute of Atmospheric Physics , Chinese Academy of sciences , beijing 100029, china 2. Commission of the National Natural science Foundation of china , beijing 100083, china 3. The center of Information science , peking university, beijing 100871, china 4. Open Laboratory of Visual Information Processing , Institute of Biophysics , Chinese Academy of sciences , beijing 100101, china State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry Institute of Atmospheric Physics Chinese Academy of Sciences Beijing China Commission of the National Natural science Foundation of china Beijing China The center of Information science Peking University Beijing China Open Laboratory of Visual Information Processing Institute of Biophysics Chinese Academy of Sciences Beijing China

Studies on brain-vision have entered a new stage, after the stimulus-induced y synchronized oscillation of neuron group activities have been discovered in cat primary visual cortex. Naturally, how to understand the visual system became a very important methodological problem. From aspects such as information processing, nonlinear dynamics and neuronal network, some primary problems in vision studies have been deeply discussed, which are

关键词： neuron group (neural population) synchro-oscillation computational theory of vision response synchroniza-tion.

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Status of study on biological and toxicological effects of nanoscale materials

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science china Chemistry 2005年第5期48卷 385-394页

作者： WANG Bing1, FENG Weiyue1, ZHAO Yuliang1, XING Gengmei1, CHAI Zhifang1, WANG Haifang2 & JIA Guang3.1. Laboratory for Bio-Environmental health sciences of Nanoscale Materials (Nanosafety Lab), Institute of High Energy Physics, Chi-nese Academy of sciences, {3. 100049, china 2. College of Chemistry and Molecular Engineering, peking university, {3. 100871, china 3. Department of Occupational and Environmental health sciences, School of Public health, peking university, {3. 100083, china 1. Laboratory for Bio-Environmental health sciences of Nanoscale Materials (Nanosafety Lab) Institute of High Energy Physics Chinese Academy of Sciences 100049 Beijing China 2. College of Chemistry and Molecular Engineering Peking University 100871 Beijing China 3. Department of Occupational and Environmental health sciences School of Public Health Peking University 100083 Beijing China

Because the physical and chemical properties of nanosized materials mostly differ from the existing microsized materials, their potential impacts on human health and the envi-ronment will be topics under the serious discussions in press and in a number of international scientific journals. We analyze and summarize the existing data of the experimental study on the biological activities and adverse effects of nanoscale materials/particles including single wall carbon nanotubes, multi wall carbon nanotubes, titanium oxide and iron powders. Though some biological behaviors of nanoscale materials observed cannot be understood on the basis of the current knowledge, as the existing data are mostly preliminary, it is too early to make some ex-clusive conclusions on biological activities (or the toxicity) of any of nanoscale materials. The experimental techniques, the current topics, and the future research directions for this new re-search field are also discussed.

关键词： nanomaterials, single wall carbon nanotubes, multi wall carbon nanotubes, titanium oxide and iron, biological activity and toxicological effect.

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Expression of PDCD5 , a novel apoptosis related protein, in human osteoarthritic cartilage

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Acta Pharmacologica Sinica 2004年第05期25卷 143-148页

作者： Ai-xin CHENG, Si-quan LOU2, Hao-wei ZHOU, Ying WANG3. Da-long MA3.epartment of Orthopaedic Surgery, Third Hospital, peking university, beijing {3. 3.4} for Human Disease Genomics, peking university, beijing {3., china Department of Orthopaedic Surgery Third Hospital Peking University center for Human Disease Genomics Peking University

AIM: To investigate the expression features of PDCD5 (programmed cell death 5 protein) in osteoarthritic andnormal human cartilage, and speculate on its potential functions in the pathogenesis of osteoarthritis (OA).METHODS: Articular cartilage specimens were obtained from 3. patients with OA and 16 healthy patients at thetime of arthroplasty. Expression of PDCD5 was detected by flow cytometry, immunofluorescence, RT-PCR andimmunohistochemical analysis. RESULTS: Enhanced expression and nuclear accumulation of PDCD5 in OAchondrocytes were found. PDCD5-positive chondrocytes were mainly distributed in the superficial and deep zonesof OA tissue sections, as opposed to, in the superficial and middle regions of normal healthy tissue ***: Since apoptotic chondrocyte death occurs more frequently in OA cartilage than in normal healthycartilage and PDCD5 is an apoptosis-related protein, the different expression patterns of PDCD5 in OA cartilagefrom that in normal healthy cartilage indicate that PDCD5 is involved in the pathogenesis of OA.

关键词： apoptosis cartilage osteoarthritis PDCD5

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Receptor subtype involved in α-adrenergic receptor-mediated Ca2+ signaling in cardiomyocytes

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Acta Pharmacologica Sinica 2007年第7期 968-974页

作者： Da-li LUO~(2,3.4),Jian GAO~2,Lin-lin FAN~2,Yu TANG~2,You-yi ZHANG~3.Qi-de HAN~3.2 Department of Pharmacology,School of Chemical Biology and Pharmaceutical sciences,Capital university of Medical sciences,{3.100069,china ~3.Institute of cardiovascular science at the health science center,peking university,{3. {13.

Aim:The enhancement of intracellular Ca2+signaling in response to α1-adrener-gic receptor （α1-AR） stimulation is an essential signal transduction event in theregulation of cardiac functions,such as cardiac growth,cardiac contraction,andcardiac adaptation to various *** present study was intended todetermine the role（s） of the α1-AR subtype（s） in mediating this ***:We evaluated the effects of subtype-specific agonists and antagonists of the α1-AR on the intracellular Ca2+signaling of neonatal rat ventricular myocytes usinga confocal ***:After being cultured for 48 h,the myocytesexhibited spontaneous local Ca2+release,sparks,and global Ca2+*** of the α1-AR with phenylephrine,a selective agonist of the α1-AR,dose-dependently increased the frequency of Ca2+transients with an EC50valueof 2.3.μmol/*** the α1A-AR subtype with 5-methylurapidil （5-Mu） inhi-bited the stimulatory effect of phenylephrine with an IC50value of 6.7 nmol/***,blockade of the α1B-AR and α1D-AR subtypes with chloroethylclonidineand BMY 73.8,respectively,did not affect the phenylephrine ***,thelocal Ca2+spark numbers were also increased by the activation of the α1-AR,andthis effect could be abolished selectively by *** importantly,A61603.anovel selective α1A-AR agonist,mimicked the effects of phenylephrine,but withmore potency (EC50value=6.9 nmol/L) in the potentiation of Ca2+transients,andblockade of the α1A-AR by 5-Mu caused abolishment of its ***:These results indicate that α1-adrenergic stimulation of intracellular Ca2+activityis mediated selectively by the α1A-AR.

关键词： α1-adrenergic receptor subtype cardiomyocyte Ca2+ signaling A61603

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