Ming Fan

Beijing Institute of Microbiology and Epidemiology, Beijing, Beijing Shi, China

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Publications (4)11.98 Total impact

  • Article: Increased neuroglobin levels in the cerebral cortex and serum after ischemia-reperfusion insults.
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    ABSTRACT: Neuroglobin (NGB) is a newly discovered protein localized in neurons of the central and peripheral nervous systems in vertebrates. It functions to bind, store, and facilitate the utilization of oxygen in neuronal cells. Recent studies suggest that it may modulate hypoxic and ischemic injury. The major goal of the present study is to characterize the dynamic changes of NGB protein in the brain and serum in a global forebrain ischemia-reperfusion model using gerbils. The sensitivity and validity of serum NGB as a potential biomarker for brain injury were further evaluated. Global cerebral ischemia-reperfusion models were induced by bilateral carotid occlusion for 20 min followed with 2-, 8-, 16-, 24-, 48-, or 72-h reperfusion in forty-six Mongolian gerbils. Sham-operated and operated animals were sacrificed at the designated time after reperfusion. Brains were fixed for immunocytochemical study to evaluate the time-dependent expression of NGB, and the concentration of NGB in serum was measured by enzyme-linked immunosorbent assay. Our results showed that the expression of NGB was upregulated in the cerebral cortex but significantly downregulated in the hippocampus from 2 to 72 h of reperfusion after 20 min of bilateral common carotid arteries occlusion. The concentration of NGB in serum was significantly increased at 8 h and reached a peak at 48 h of reperfusion. There is a significant correlation between NGB levels in the serum and severity of neuronal damage in the gerbil brain. In summary, the upregulation of NGB in cerebral cortex and downregulation in hippocampus after reperfusion insults in the gerbil brain are consistent with the fact that cerebral cortex is more tolerant to hypoxic or ischemic injury than the hippocampus. Moreover, the changes of NGB levels in serum may be used to monitor the extent of brain damage in ischemic brain diseases.
    Brain Research 04/2006; 1078(1):219-26. · 2.73 Impact Factor
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    Article: Identification of a novel alternative splicing form of human netrin-4 and analyzing the expression patterns in adult rat brain.
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    ABSTRACT: Netrins are a family of secreted proteins that function as tropic cues directing axon growth and cell migration during neural development. Beta-netrin or netrin-4 (NTN4), the fourth member of this family, was previously reported by Koch (M. Koch, J.R. Murrell, D.D. Hunter, P.F. Olson, W. Jin, D.R. Keene, W.J. Brunken, R.E. Burgeson. A novel member of the netrin family, beta-netrin, shares homology with the beta chain of laminin: identification, expression, and functional characterization. J. Cell Biol. 151 (2000) 221-234) and Yin (Y. Yin, J.R. Sanes, J.H. Miner, Identification and expression of mouse netrin-4. Mech. Dev. 96 (2000) 115-119), respectively. However, whether there is another isoform of netrin-4 and the expression patterns have not been fully determined. Here we report the cloning of a novel isoform of human netrin-4 using rapid amplification of complementary DNA (cDNA) ends (RACE) technique and analysis on the netrin-4 mRNA expression in adult rat brain using in situ hybridization. The new isoform lacks the signal peptide region and might represent a truncated form at the Laminin-N terminal domain of human netrin-4. Examination of the expression pattern of netrin-4 mRNA in adult rat brain revealed that the netrin-4 mRNA was widely expressed in many regions of the brain. High levels of netrin-4 mRNA was found in the pyramidal cell layer of the cerebral cortex, prepiriform cortex, amygdaloid nuclei, pyramidal layer of hippocampus, Purkinje's cells, medial cerebellar nucleus and interposed cerebellar nucleus, medial nucleus of the trapezoid body and mitral cell layer of the olfactory bulb. Moderate signals were present in frontal cortex, several thalamic and hypothalamic nuclei. The widespread expression of netrin-4 in adult rat brain indicates that netrin-4 is not only important for axon guidance during embryonic development, but also critical to neuronal plasticity in adult stage.
    Molecular Brain Research 12/2004; 130(1-2):68-80. · 2.00 Impact Factor
  • Article: Identification, characterization, and functional study of the two novel human members of the semaphorin gene family.
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    ABSTRACT: We cloned two novel human transmembrane semaphorins, (HSA)SEMA6C and (HSA)SEMA6D, that belong to the class VI subgroup of the semaphorin family. The genes for SEMA6C and SEMA6D are mapped on chromosome 1q12-21.1 and 15q21.1, respectively. Among the adult tissues, SEMA6C is expressed only in skeletal muscle, whereas SEMA6D is expressed abundantly in kidney, brain, and placenta and moderately in the heart and skeletal muscles. During murine development, neither SEMA6C nor SEMA6D was expressed in embryonic day 10.5 (E10.5) embryos, but both were highly expressed in the areas of the lateral ventricle, the striatum, the wall of the midbrain, the pons/midbrain junction, and the choroid plexus of E13 embryos. Were neurons, neither axons nor astrocytes, highly expressed both semaphorins. Three isoforms of SEMA6C and five isoforms of SEMA6D derived from alternative splicing were identified, and their expression was regulated in a tissue- and development-dependent manner. Deletion analysis indicated that a sema domain and a PSI domain are integrally necessary for correct post-translation modification and subcellular localization. The extracellular domain of SEMA6C inhibited axonal extension of nerve growth factor-differentiated PC12 cells and induced the growth cone collapse of chicken dorsal root ganglion, rat hippocampal neurons, and rat cortical neurons in a dose-responsive manner. SEMA6D acted like SEMA6C except it had no significant effect on the growth cones of rat cortical neurons.
    Journal of Biological Chemistry 10/2002; 277(38):35574-85. · 4.77 Impact Factor
  • Article: Full-length cDNA cloning of human neuroglobin and tissue expression of rat neuroglobin.
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    ABSTRACT: Neuroglobin is a recently discovered respiratory, porphyrin-containing protein that is expressed in the brain of mouse and human. However, the full-length cDNA sequence and genomic organization of human neuroglobin have not been reported. In this paper, the full-length cDNA sequence of human neuroglobin was cloned following bioinformatic analysis and the rapid amplification of cDNA ends (RACE) technique. It was shown that the full-length cDNA sequence (GenBank Accession No. AF422796) of human neuroglobin is 1909 bp in size, and the genomic sequence is 8041 bp in size (GenBank Accession No. AF422797). To further study the characterization of this gene, the coding region of rat neuroglobin (GenBank Accession No. AF333245) was cloned by using degeneracy PCR. The result showed high conservation among human, rat, and mouse neuroglobin. Furthermore, it was demonstrated that NGB was extensively expressed in rat brain by using in situ hybridization and the immunohistochemical technique. Transcription of NGB mRNA was shown to be widely distributed throughout the adult rat brain, including cerebral cortex, hippocampus, thalamus, hypothalamus, olfactory bulb, and cerebellum. NGB protein immunoreactive cells were also widely distributed throughout normal adult rat brain, including cerebral cortex, hippocampus, thalamus, hypothalamus, pons, and cerebellum. It could be seen that the NGB-immunopositive signals were in the cytoplasma and processes of the neuron. These data strongly support the notion that neuroglobin is a highly conserved gene in evolution and is very important in the nervous system, possibly related to the oxygen supply of the neuron.
    Biochemical and Biophysical Research Communications 03/2002; 290(5):1411-9. · 2.48 Impact Factor

Institutions

  • 2002–2004
    • Beijing Institute of Microbiology and Epidemiology
      Beijing, Beijing Shi, China
    • Chinese National Human Genome Center at Shanghai
      Shanghai, Shanghai Shi, China