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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~32 department of pharmacology,school of chemical biology & pharmaceutical sciences,capital university of medical sciences,beijing 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,beijing 100871,china department of pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing China Institute of Cardiovascular Science at Health Science Center Peking University Beijing China Institute of Molecular Medicine and College of life Science Peking University Beijing 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（IP3Rs）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3Rsmay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3Rs was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3BM）,a membrane-permeant ester of IP3,to activate IP3Rs directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3BM(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,IP3R inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3BM-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3H]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3R 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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Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2020年第1期41卷 3-19页

作者： Pei Zhang Jie-Si Chen qi-Ye li Long-Xiang sheng Yi-Xing gao Bing-Zheng Lu Wen-Bo Zhu xiao-Yu Zhan Yuan li Zhi-Bing Yuan gang Xu Bi-Tao qiu Min Yan Chun-Xue Guo You-qiong wang Yi-Jun Huang Jing-Xia Zhang Fu-Yu liu Zhong-wei Tang Sui-Zhen lin david NCooper Huan-Ming Yang jian wang Yu-qi gao wei Yin Guo-Jie Zhang Guang-mei Yan State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China BGI-Shenzhen ShenzhenGuangdong 518083China Section for Ecology and Evolution Department of BiologyUniversity of CopenhagenCopenhagen DK-2100Denmark department of pharmacology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Institute of Medicine and Hygienic Equipment for High Altitude Region College of High Altitude Military MedicineThird Military Medical UniversityChongqing 400038China Key Laboratory of High Altitude Medicine of People's liberation Army Chongqing 400038China Key Laboratory of High Altitude Environmental Medicine Third Military Medical UniversityMinistry of EducationChongqing 400038China school of pharmaceutical sciences Sun Yat-Sen UniversityGuangzhouGuangdong 510006China Guangzhou Cellprotek pharmaceutical Co.Ltd. GuangzhouGuangdong 510663China Institute of medical Genetics School of MedicineCardiff UniversityCardiff CF144XNUK James D.Watson Institute of Genome sciences HangzhouZhejiang 310058China department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China china National Genebank BGI-ShenzhenShenzhenGuangdong 518120China

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

关键词： Acute hypobaric hypoxia Cynomolgus monkeys Brain injury Neuroprotectant Gene regulatory networks

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Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2021年第2期42卷 250-251页

Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial license(http:1/***/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,*** reprodu... 详细信息

关键词： Open Creative Access

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