常彦忠
在机体铁吸收、转运、储存、利用的调控,脑铁代谢的分子机制与神经退行性疾病,神经损伤的保护等基础和应用研究方面取得了重要的研究成果
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- 姓名:常彦忠
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学术头衔:
博士生导师
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学科领域:
神经生物学
- 研究兴趣:在机体铁吸收、转运、储存、利用的调控,脑铁代谢的分子机制与神经退行性疾病,神经损伤的保护等基础和应用研究方面取得了重要的研究成果
常彦忠博士,教授,博士研究生导师, 中国生物物理学会自由基生物学与自由基医学专业委员会专业委员。1987年7月毕业于河南师范大学生物学系,获理学学士学位。1989年9月至1990年10月在北京医科大学(现北京大学医学中心)生理学系科研进修,1994年2月赴新加坡国立大学分子动物学系访问,1996年9月进入北京大学医学中心生理学系攻读硕士,1999年7月获理学硕士学位。2000年8月赴香港理工大学铁代谢研究室攻读博士学位,2003年11月获哲学博士学位。同年12月任河北师范大学生命科学学院教授,河北师范大学-香港理工大学分子神经生物学与神经药理学研究所副所长,铁代谢分子生物学研究室主任,2004年成立河北师范大学生物制药研究中心,任中心主任。
1989-1999主要从事中枢神经系统对心血管活动调节机理方面的研究工作。2000年以来,在机体铁吸收、转运、储存、利用的调控,脑铁代谢的分子机制与神经退行性疾病,神经损伤的保护等基础和应用研究方面取得了重要的研究成果。在本学科(生理学)国际影响力最高的研究刊物上(Journal of Cellular Physiology)发表论文3篇,目前在国际刊物(SCI收录)发表论文16篇,在国内期刊上发表论文40余篇,申请国家发明专利4项,其中2项已获批,2项已公开。1995年5月获国家教育委员会科技进步三等奖,1996年12月获北京医科大学科技成果奖,2004年获河北省优秀发明者称号,2006获河北省自然科学三等奖。先后参与完成两项国家自然科学基金,两项香港科技资助局基金项目,一项卫生部基金项目,目前,主持国家自然科学基金1项,中国博士后科研基金1项, 河北省自然科学基金2项,河北省科技厅、教育厅、石家庄市、学校研究基金等5项。指导博士研究生、硕博连读生共5人,硕士研究生7人。2007年被遴选为河北省首批百名创新人才支持计划。
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【期刊论文】Ceruloplasmin expression and its role in iron transport in C6 cells
常彦忠, Yan Zhong Changa, Zhong Ming Qian, , Jin Rong Du, Li Zhu, Youjia XU, Lian-Zhi Li, Chen-Yuen Wang, Qin Wang, Xiao Hu Ge, Kwok Ping Ho, Lijin Niu, Ya Ke
Y. Z. Chang et al. Neurochemistry International 50 (2007) 726-733,-0001,():
-1年11月30日
Ceruloplasmin (CP) is essential for brain iron homeostasis. However, little is known about the effect of iron on CP expression in the brain. Also, the role of CP in brain iron transport has not been well determined. In this study, we investigated the effects of iron on CP expression and the role of CP in iron transport in the C6 rat glioma cells. Our data showed that treatment of the cells with iron (cell iron overload) or iron chelators (cell iron deficiency) did not induce a significant change in the expression of CP mRNA. However, western blotting analysis demonstrated that cell iron overload induced a significant decrease in CP protein content in the cells and that treatment with iron chelators led to a significant increase in CP protein level in the cells. These findings suggest a translational regulation of CP expression by iron in the cells. We also examined the effects of CP on iron transport in the cells. We found that glycosylphosphatidylinositol-anchored CP did not have any impact on iron uptake by normal iron or iron-deficient cells nor on iron release from normal iron or iron-sufficient cells. However, low concentrations of soluble CP (2-8μg/ml) increased iron uptake by iron-deficient C6 glioma cells, while the same concentrations of CP had no effect on iron uptake by normal iron cells and iron release from normal iron and iron-sufficient cells. The possible reason for the difference between our results in vitro and those obtained from in vivo studies was discussed.
Cerulopalsmin, Gene expression, Iron deficiency, Iron overload, Iron uptake and release, C6 glioma cells, Brain iron homeostasis
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常彦忠, Yan-Zhong Chang, Ya Ke, , Jun-Rong Du, Georges M. Halpern, Kwok-Ping Ho, Li Zhu, Xiao-Song Gu, You-Jia Xu, Qin Wang, Lian-Zhi Li, Chen-Yuen Wang, and Zhong-Ming Qian
Molecular Pharmacology Vol. 69, No. 3,-0001,():
-1年11月30日
Based on the available data, we speculated that changes in brain iron metabolism induced by L-DOPA might be associated with the neurotoxicity of L-DOPA. To investigate this possibility, the effects of L-DOPA on the expression of iron influx proteins [transferrin receptor (TfR) and divalent metal transporter 1 (DMT1)], iron efflux protein (ferroportin 1), and iron uptake in C6 glioma cells were determined in this study using Northern blot and Western blot analysis and the calcein method. The findings showed that treatment of C6 cells with different concentrations of L-DOPA (0-100 AM) did not affect the expression of mRNA and protein of TfR and DMT1 with iron-responsive element (+IRE) and protein of ferroportin 1. However, a significant increase in the expression of DMT1(-IRE) mRNA and protein was found in cells treated, respectively, with 10 and 30μM L-DOPA (mRNA) and 1, 5, 10 and 30μM L-DOPA (protein). The increase in DMT(-IRE) protein induced by L-DOPA treatment was in parallel with the increase in DMT(-IRE) mRNA. The levels of DMT1(-IRE) mRNA and protein peaked in the cells treated with 10 AM L-DOPA and then decreased progressively with increasing concentrations of L-DOPA. Further study demonstrated that treatment of the cells with 10 AM L-DOPA induced a significant increase in ferrous uptake by C6 glioma cells. The findings suggested that the increased DMT1 (-IRE) expression might be partly associated with the neurotoxicity of L-DOPA. Clinical relevance of the findings needs to be investigated further.
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【期刊论文】Molecular analysis of increased iron status in moderately exercised rats
常彦忠, Yu Qian Liu, Xiang Lin Duan, , Yan Zhong Chang, Hai Tao Wang, and Zhong Ming Qian
Molecular and Cellular Biochemistry 282: 117-123, 2006,-0001,():
-1年11月30日
Although iron plays a critical role in exercise, the regulatory mechanism of iron metabolism remains poorly understood. The aims of the present study were to investigate the effects of different intensity exercise on body iron status and the regulatory mechanism of duodenal iron absorption. Thirty female Sprague-Dawley rats (90-100g) were randomly divided into three groups: a control group (remained sedentary, CG), a moderately exercised group (swam 1.5h/day, MG) and a strenuously exercised group (swam with different load, SG). Serum iron status, serum ferritin and Hct were examined after 10 weeks of swimming. Western blot was performed to detect the expression of iron transport proteins: divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN 1) in duodenal epithelium. The expression of hepcidin mRNA in liver was examined by RT-PCR. The results showed: (1) the body iron status in MG was kept at a high level compared to that of CG and SG, (2) Western blot showed DMT1 with iron responsive element (IRE) and FPN 1 in duodenal epithelium which were higher in MG than that of CG and (3) the expression of hepatic hepcidin mRNA was down regulated in MG (p<0.05). The data suggested that moderate exercise improved iron status and that was likely regulated by increased DMT1 with IRE and FPN 1 expression. Hepcidin signaling pathway may involve in the regulation of duodenal iron absorption proteins.
divalent metal transporter 1: duodenal epithelium, ferroportin 1, hepcidin, iron absorption
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【期刊论文】Effects of Development and Iron Status on Ceruloplasmin Expression in Rat Brain
常彦忠, YAN ZHONG CHANG, ZHONG MING QIAN, , KUI WANG, LI ZHU, XIAO DA YANG, JIN RONG DU, LIN JIANG, KWOK PING HO, QIN WANG, AND YA KE
JOURNAL OF CELLULAR PHYSIOLOGY 204: 623-631 (2005),-0001,():
-1年11月30日
The increased iron content in the brain of subjects with aceruloplasminemia has implicated ceruloplasmin (CP) as a major factor in the regulation of regional brain iron content. In this study, we investigated the effects of age and iron on CP expression in rat brain. In al I four regions, the iron concentrations increased with developmental age. There is a similar trend in age-induced changes in CP mRNA and protein. The CP mRNA and protein levels were both lowest at postnatal day (PND) 7. The expression increased gradually with age, reaching the highest at PND 196 in the striatum and substantia nigra, and at PND 21 and PND 63 in the cortex and hippocampus, respectively. This suggests the existence of an age-dependent pre-transcriptional regulation and a regionally specific effect of age on CP expression in the brain. Although total iron in all four regions was significantly lower in the rats fed with a low-iron diet for 6 weeks and higher in the rats with a high-iron diet than those in the control animals, no significant between-group differences i n CP mRNA and protein were found in these animals, except in the substantia nigra where a significant increase i n CP protein in high-iron rats was observed, and the reverse in low-iron rats. These findings suggested that the effects of iron on CP expression in the brain may be region-specific, and that regulation of CP expression by iron in the substantia nigra was at the post-transcriptional level.
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常彦忠, Ya Ke, , Yan Zhong Chang, Xiang Lin Duan, Jin Rong Du, Li Zhu, Kui Wang, Xiao Da Yang, Kwok Ping Ho, Zhong-ming Qian
Y. Ke et al. Neurobiology of Aging 26 (2005) 739-748,-0001,():
-1年11月30日
The DMT1 (Nramp2/DCT1) is a newly discovered proton-coupled metal-ion transport protein. The cellular localization and functional characterization of DMT1 suggest that it might play a role in physiological iron transport in the brain. In the study, we evaluated effects of dietary iron and age on iron content and DMT1 expression in four brain regions: cortex, hippocampus, striatum, substantia nigra. Total iron content in all regions was significantly lower in the low-iron diet rats and higher in the high-iron diet rats than that in the control animals, showing that dietary iron treatment for 6-weeks can alter brain iron levels. Contrary to our expectation, there was no significant alternation in DMT1(+IRE) and (-IRE) mRNA expression and protein content in all brain regions examined in spite of the existence of the altered iron levels in these regions after 6-weeks' diet treatment although TfR mRNA expression and protein level were affected significantly, as was expected. The data demonstrates that expression of DMT1(+IRE) and (-IRE) was not regulated by iron in these regions of adult rats. The lack of response of DMT1 to iron status in the brain suggests that the IRE of brain DMT1 mRNA might be not really iron-responsive and that DMT1-mediated iron transport might be not the rate-limiting step in brain iron uptake in adult rats. Our findings also showed that development can significantly affect brain iron and DMT1(+IRE) and (-IRE) expression but the effect varies in different brain regions, indicating a regionally specific regulation in the brain.
Brain iron metabolism, DMT1 (, Nramp2/, DCT I), expression, Age and iron status, Brain regions
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【期刊论文】Expression of ferroportin 1, hephaestin and ceruloplasmin in rat heart
常彦忠, Zhong Ming Qian, , Yan Zhong Chang, Gina Leung, Jun Rong Du, Li Zhu, Qin Wang, Lijian Niu, You Jia Xu, Lei Yang, Kwok Ping Ho, Ya Ke
Z. M. Qian et al. Biochimica et Biophysica Acta 1772 (2007) 527-532,-0001,():
-1年11月30日
Iron-mediated injury plays an important role in a number of heart disorders. Studies on heart iron are therefore crucial for understanding the causes of excessive heart iron. Heart cells have the ability to accumulate transferrin-bound-iron via the transferrin receptor and non-transferrin-bound-iron probably via the L-type Ca2+ channel and the divalent metal transporterl. However, little is known about the mechanisms of iron export in the heart cells. Here, we investigated expression of iron exporters including ferroportin 1 (Fpnl), ceruloplasmin (CP) and hephaestin (Heph) and provided evidence for their existence in the heart. We demonstrated that iron has a significant effect on expression of Fpnl and CP, but not Heph. Treatment of a high-iron diet induced a significant increase in Fpnl, a decrease in CP but no change in Heph mRNA and protein. The control of Fpnl and CP protein expression by iron was parallel to that of their mRNA expression, suggesting a transcriptional regulation of Fpnl and CP by iron. The existence of these proteins in the heart implies that they might have a role in heart iron homeostasis.
Ferroportin 1, Ceruloplasmin, Hephaestin, Transferrin receptor, Heart, Iron metabolism
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【期刊论文】Post-Transcriptional Expression of DMT1 in the Heart of Rat
常彦忠, YA KE, YIN YIN CHEN, YAN ZHONG CHANG, , XIANG LIN DUAN, KWOK PING HO, DE HE JIANG, KUI WANG, ZHONG MING QIAN
JOURNAL OF CELLULAR PHYSIOLOGY 196: 124-130 (2003),-0001,():
-1年11月30日
Non-transferrin-bound iron (NTBI) overtaken by heart cells might be a key cause leading to iron-mediated injury in heart disorders. NTBI uptake by heart cells might be mediated by divalent metal transporter 1 (DMT1). The understanding of the role of DMT1 in heart iron metabolism is fundamental for elucidating the cause resulting in excessive iron in the heart. The study was to evaluate effects of age and dietary iron on DMT1 mRNA expression and protein synthesis in rat heart. DMT1 mRNA expression was determined by RT-PCR and sequence analysis, and DMT1 protein by Western blot analysis. DMT1 mRNAs with or without iron-responsive element (IRE) both were found in rat heart. Expression of two forms of DMT1 mRNAs was the lowest at the age of post-natal day (PND) 7, and then increased with the age, reaching the highest at PND196 (non-IRE form) and PND63 (IRE form), respectively. During different ages, the levels of DMT1 (IRE) mRNA were higher than those of DMT1 (non-IRE) mRNA and were significantly correlated with the non-heme iron contents in the heart. After fed a high iron for 6 weeks, the rats had a sixfold elevation in heart iron and 22% (non-IRE from) and 40% (IRE from) reduction in DMT1 protein compared to the controls. A low iron diet for 6-weeks caused cardiac hypertrophy and heart iron deficiency and also an increase in levels of two forms of DMT1 proteins. However, iron status had no significant effect on DMT1 (IRE) and DMT1 (non-IRE) mRNAs expression in the heart, although it can significantly influence heart transferrin receptor (TfR) mRNA expression. The results demonstrated that DMT1 mRNAs expression in the heart is age-dependent and that two forms of DMT1 mRNAs both are regulated by iron on the post-transcriptional level only.
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常彦忠, 段相林, , 钱忠明
生物化学与生物物理进展Prog. Biochem. Biophys. 2003; 30 (4),-0001,():
-1年11月30日
转铁蛋白受体2 (transferrin receptor 2,TfR2)是最近发现的一种重要铁代谢蛋白.研究显示它不仅是一种介导肝脏细胞铁摄取的主要蛋白,而且在调节小肠铁吸收方面起着极其关键的作用,是控制肝脏铁调素合成和释放的关键成分,已经证实,Tf R2基因突变是遗传性血色素沉着病的重要原因之一.
铁代谢, 转铁蛋白受体2, 铁吸收, 遗传性血色素沉着
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【期刊论文】Distribution of Ferroportin 1 Protein in Different Regions of Developing Rat Brain
常彦忠, Dai He Jiang, Ya Ke, Yan Zhong Cheng, Kwok Pin Ho, Zhong M ing Qian
Dev Neurosci 2002; 24: 94-98,-0001,():
-1年11月30日
Ferroportin 1 is a newly discovered transmembrane iron export protein. It plays a key role in Fee+transport across the basal membrane of enterocytes in the gut. It has been suggested that this protein might have the same role in Fee+transport across the abluminal membrane of the blood-brain barrier as it works in enterocytes. However, the presence of ferroportin 1 in the brain has not been well determined. In the present study, we investigated expression of ferroportin 1 protein in different brain regions, including cortex, hippocampus, striatum and substantia nigra, in developing male Sprague-Dawley rats. The results provided direct evidence for the existence of ferroportin 1 protein in the rat brain. All brain areas examined have the ability to synthesize ferroportin 1 protein. The findings also showed that age has a significant effect on the expression of ferroportin 1 protein in the cortex, hippocampus, striatum and substantia nigra of the rat brain.
Ferroportin 1 protein, Brain iron metabolism, Developing SD rat, Cortex, Hippocampus, Striatum, Substantia nigra
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常彦忠, Yun-Hui Ku, Yan-Zhong Chang
Y. -H. Ku, Y. -Z. Chang. Peptides 22 (2001) 1465-1470,-0001,():
-1年11月30日
It has been proved that input of specific electroacupuncture (EA) can activate β-endorphin(β-EP)ergic and noradrenergic neurons projecting to the rostral ventrolateral medulla (RVL), the latter acting upon the RVL-GABAergic interneurons, thereby produce depressor effect. The present study further shows that: (1) The EA depressor effect is strong enough to surpass the pressor response of the AC (nucleus amygdaloideus centralis)-emotional circuit, (2) both β-endorphin (β-EP) and GABA in the RVL mediate the EA antagonistic effect, (3) the EA effect does not take place in the AC and paraventricular nucleus (two key nuclei besides the RVL, which also have β-EPergic input) in the emotional circuit.
Blood pressure, Emotion, Stress, Central nervous system, β-Endorphin, GABA, Acupuncture
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