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An EGLN1 mutation may regulate hypoxic response in cyanotic congenital heart disease through the PHD2/HIF-1A pathway

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Genes & Diseases 2019年第1期6卷 35-42页

作者： Yuanlin Zhou Na Ouyang Lingjuan Liu Jie Tian xupei huang Tiewei Lu Department of Cardiology Children’s Hospital of Chongqing Medical UniversityChongqingPR China Key Laboratory of Developmental Disease in Childhood(Chongqing Medical University) Ministry of EducationChongqingPR China Key Laboratory of Pediatrics in Chongqing ChongqingPR China Chongqing International Science and Technology Cooperation Center for Child Development and Disorders ChongqingPR China Department of Biomedical Science Charlie E.Schmidt College of MedicineFlorida Atlantic UniversityBoca RatonFLUSA

Cyanotic congenital heart disease(CCHD),a term describing the most severe congenital heart diseases are characterized by the anatomic malformation of a right to left *** the incidence of CCHD are far less than the that of congenital heart diseases(CHD),patients with CCHD always present severe clinical features such as hypoxia,dyspnea,and heart *** hypoxia induces hypoxemia that significantly contributes to poor prognosis in *** studies have demonstrated that the prolyl-4-hydroxylase2(PHD2,encoded by EGLN1)/hypoxia-inducible factor-1A(HIF-1A)pathway is a key regulator of hypoxic ***,we aim to assess the associations of single polymorphisms(SNPs)of the EGLN1 gene and hypoxic response in CCHD.A missense variant of EGLN1 c.380G>C(rs1209790)was found in 46 patients(46/126),with lower hypoxia incidence and higher rate of collateral vessel formation,compared with the wild type(PC showed improved response to hypoxia compared with the wild-type *** EGLN1 c.380G>C mutation improves hypoxic response through the PHD2/HIF-1A pathway,which may provide a molecular mechanism for hypoxic response in *** effects of the EGLN1 c.380G>C mutation on CCHD prognosis deserve further investigation.

关键词： Cyanotic congenital heart disease EGLN1 Hypoxic response Mutation Polymorphism

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Epigenetic regulation of phosphodiesterase 4d in restrictive cardiomyopathy mice with cTnI mutations

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Science China(Life Sciences) 2020年第4期63卷 563-570页

作者： Weian Zhao Xiaoqi Wu Zhiyuan Wang Bo Pan Lifei Liu Lingjuan Liu xupei huang Jie Tian Department of Cardiology Heart CentreChildren’s Hospital of Chongqing Medical UniversityMinistry of Education Key Laboratory of Child Development and DisordersKey Laboratory of Pediatrics in ChongqingChongqing International Science and Technology Cooperation Center for Child Development and DisordersChongqing 400014China Department of anesthesiology The Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Biomedical Science Charlie E.Schmidt College of MedicineFlorida Atlantic UniversityBoca Raton 33414USA

Epigenetic regulations play an important role in disease *** this study,we have investigated epigenetic regulations in restrictive cardiomyopathy mice with cTnI 193 His *** results demonstrated that phosphodiesterase(PDEs)4d was down-regulated in the heart of these *** studies showed that the epigenetic modifications were associated with enhanced acetylation of histone 3 lysine 4 and lysines 9,whereas tri-methylation of histone 3 lysine 4,were decreased in histones near the PDE4d gene promoter *** binding levels of histone transmethylase SMYD1 and histone deacetylase HDAC1 were increased in the gene promoter regions in cTnI193 His transgenic *** immune-fluorescent labeling we found an evidence of cTnI existence in the nucleus of cardiomyocytes and Western blotting further confirmed that both wild type and mutated cTnI could be detected in the cell nucleus of the ***,an interaction between cTnI and SMYD1,or cTnI and HDAC1 was *** of the mutated cTnI in cultured cardiomyocytes reduced the expression of *** data suggest that the decrease of PDE4d expression in RCM mice caused by cTnI mutations may be related to epigenetic regulation,i.e.,histone acetylation and methylation,and cTnI might be involved in this procedure via an interaction with HDAC1 and SMAD1 in the hearts.

关键词： phosphodiesterase epigenetics histone modifications restrictive cardiomyopathy cardiac troponinⅠ

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Acetylation of H3K4,H3K9,and H3K27 mediated by p300 regulates the expression of GATA4 in cardiocytes

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Genes & Diseases 2019年第3期6卷 318-325页

作者： Wei Zhou Dagui Jiang Jie Tian Lingjuan Liu Tiewei Lu xupei huang Huichao Sun Heart Centre Children’s Hospital of Chongqing Medical UniversityMinistry of Education Key Laboratory of Child Development and DisordersChongqing400014China China International Science and Technology Cooperation Base of Child Development and Critical Disorders Chongqing400014China Chongqing Key Laboratory of Pediatrics Chongqing400014China Department of Biomedical Science Charlie E.Schmidt College of MedicineFlorida Atlantic UniversityBoca RatonFLUSA Heart Centre Children’s Hospital of Chongqing Medical UniversityChongqing400014China

GATA4 is a particularly important cardiogenic transcription factor and serves as a potent driver of *** progress in the field has made it clear that histone acetylation can influence gene expression through changing the structure of *** previous research had revealed that hypo-acetylation could repress gata4 expression in cardiocytes,however the underlying mechanism by which this occurred was still *** reveal the mechanism of histone acetylation involved in the regulation of gata4 transcription,we concentrated on P300,one of the important histone acetyltransferase associated with *** found that P300 participated in gata4 expression through regulating histone acetylation in embryonic mouse ***-mediated downregulation of P300 modulated the global acetylation of H3 and the acetylation of H3K4,H3K9,and H3K27 in gata4 and Tbx5 ***,there was an obvious inhibition of gata4 transcription,whereas Tbx5 was not ***,SGC-CBP30,the selective inhibitor of the bromodomain in CBP/P300,downregulated gata4 transcription by repressing the acetylation of H3K4,H3K9,and H3K27 in the gata4 *** together,our results identified that acetylation of H3K4,H3K9,and H3K27 mediated by P300 plays an important role in regulation of gata4 expression in cardiogenesis.

关键词： gata4 P300 Acetylation H3K4ac H3K9ac H3K27ac

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Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes

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Genes & Diseases 2022年第6期9卷 1689-1700页

作者： Qian Lu Bo Pan Haobo Bai Weian Zhao Lingjuan Liu Gu Li Ruimin Liu Tiewei Lv xupei huang Xi Li Jie Tian Department of Pediatric Cardiology Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014PR China Chongqing Key Laboratory of Pediatrics Chongqing 400014PR China Department of Orthopedic The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Department of Biomedical Science Charlie E.Schmidt College of MedicineFlorida Atlantic UniversityBoca RatonFL 33431USA Biology Science Institutes of Chongqing Medical University Chongqing 400016PR China

In the past studies,it is shown that cardiac troponin I(cTnI,encoded by TNNI3),as a cytoplasmic protein,is an inhibitory subunit in troponin complex,and involves in cardiomyocyte diastolic ***,we assessed a novel role of cTnI as a ***,the nuclear translocation of cTnI was found in mouse,human fetuses and rat heart *** addition,there were differences in percentage of intranuclear cTnI in different *** on weighted gene co-expression network analyses(WGCNA)and verification in cell experiments,a strong expression correlation was found between TNNI3 and Atp2a2,which encodes sarco-endoplasmic reticulum Ca2t ATPase isoform 2a(SERCA2a),and involves in ATP hydrolysis and Ca2t ***3 gain and loss caused Atpa2a2 increase/decrease in a dosedependent manner both in mRNA and protein levels,in vivo and in *** using ChIP-sequence we demonstrated specific binding DNA sequences of cTnI were enriched in ATP2a2 promoter239we889 region and the specific binding sequence motif of cTnI was analyzed by software as"CCAT",which has been reported to be required for YY1 binding to the promoter region of YY1-related ***,it was further verified that pcDNA3.1()-TNNI3 could express cTnI proteins and increase the promoter activity of Atp2a2 through luciferase report *** the end,we evaluated beat frequencies,total ATP contents,Ca2t transients in TNNI3-siRNA myocardial *** findings indicated,for the first time,cTnI may regulate Atp2a2 in cardiomyocytes as a co-regulatory factor and participate in the regulation of intracellular Ca ions.

关键词： Atp2a2 Ca ions Intranuclear cardiac troponin I Nuclear translocation YY1

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Contractile protein troponin I:Physiological roles in cardiac function and its gene regulation during heart development

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中国病理生理杂志 2000年第10期 85-85页

作者： xupei.huang,Larry.F.Lemanski,Jeffery.W.Walker DepartmentofMedicalPhysiology!TexasA&MUniversitySystemHSC CollegeStation TX77843 DepartmentofMedicalPhysiology!TexasA&MUniversitySystemHSC CollegeStation TX77843 DepartmentofPhysiology!UniversityofWisconsin Madison WI53706

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Explore the treatment for restrictive cardiomyopathy and diastolic dysfunction

Explore the treatment for restrictive cardiomyopathy and dia...

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中国药理学会药学监护专业委员会第一届第三次学术大会

作者： xupei.huang College of Biomedical Science and Center for Molecular Biology and Biotechnology,Florida Atlantic University,Boca Raton,FL 33431,USA

Cardiovascular disease is the leading cause of mortality *** heart failure is a growing public health problem:it affects 4.8 million Americans and 500,000 new cases are diagnosed each *** cardiomyopathies represent a clinically diverse group of progressive heart muscle disease that can be caused by mutations in specific sarcomefic genes.A

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Mouse models for restrictive cardiomyopathy due to cTnI mutation and cTnI deficiency

Mouse models for restrictive cardiomyopathy due to cTnI muta...

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生物学时代新药研发进展研讨会

作者： xupei huang Department of Biomedical Sciences Center for Molecular Biology and Biotechnology Florida Atlantic University Advances on New Drug Research in the Era of Biological Science Chongqing, China, Nov.8,2006

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应用5----碘脱氧尿苷和5----溴脱氧尿苷进行活体SCE试验的比较

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南京医学院学报 1985年第4期 285-286页

作者：黄旭培王小萍许娟华姜一心南京医学院卫生系劳动卫生教研室南京医学院卫生系劳动卫生教研室

实验测定给予不同的卤代胸腺嘧啶核苷同类物——5-溴脱氧尿苷(BrdU)和5-碘脱氧尿苷(IdU)后小鼠骨髓细胞姊妹染色单体交换(SCE)的频率,来比较这两种药物进行活体SCE检测效果。结果表明,和BrdU一样,IdU也可用于活体SCE检测,这两种药物诱... 详细信息

实验测定给予不同的卤代胸腺嘧啶核苷同类物——5-溴脱氧尿苷(BrdU)和5-碘脱氧尿苷(IdU)后小鼠骨髓细胞姊妹染色单体交换(SCE)的频率,来比较这两种药物进行活体SCE检测效果。结果表明,和BrdU一样,IdU也可用于活体SCE检测,这两种药物诱导活体骨髓细胞SCE频率基本是相似的。

关键词： 5-碘脱氧尿苷 5-澳脱氧尿苷姊妹染色体交换鼠

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职业性铅中毒患者细胞染色体畸变和SCE分析

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工业卫生与职业病 1986年第5期 263-265页

作者：黄旭培王小萍许娟华汪鼎禄南京医学院卫生系重庆医学院卫生学教研室

我们对7例职业性铅中毒病人和7例正常人进行了外周血淋巴细胞染色体畸变和SCE分析。结果表明:铅中毒患者血铅值、EPP等明显增高;染色体畸变率和SCE率与对照组相比,均有非常显著性差异(P<0.01)。

关键词：染色体畸变外周铅中毒 SCE 患者细胞

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铅对小鼠生殖细胞染色体的影响

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南京医学院学报 1985年第2期 114-117页

作者：黄旭培许娟华王小萍冯致英翟为雷南京医学院卫生系劳动卫生学教研室南京医学院卫生系劳动卫生学教研室进修生

4组雄性小鼠自由饮用含醋酸铅0、500、1000、2000ppm的水连续50天后,测得其平均血铅值分别为12、42、71和87μg/dL。用BrdU体内实验方法作精原细胞染色体制片观察染色体畸变率和姊妹染色单体互换率。结果提示:雄性小鼠长时间接触高剂量... 详细信息

4组雄性小鼠自由饮用含醋酸铅0、500、1000、2000ppm的水连续50天后,测得其平均血铅值分别为12、42、71和87μg/dL。用BrdU体内实验方法作精原细胞染色体制片观察染色体畸变率和姊妹染色单体互换率。结果提示:雄性小鼠长时间接触高剂量的醋酸铅可能导致对生殖细胞遗传物质某些损伤效应。

关键词：醋酸铅小鼠,精原细胞 5-溴脱氧尿嘧啶核苷染色体畸变姊妹染色单体交换

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