Biomedical subjects

Guohan Hu

Publications and source records attributed to Guohan Hu.

7 recordsLinked to original sources

PubMed2005

Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas.

Gliomas are major tumors of the central nervous system with a wide spectrum of different tumor types. Ligand of Numb protein X (LNX) is PDZ domain containing protein that interacts with cell fate determinant Numb. cDNA microarray analysis was used to determine the expression of 13,939 genes in a set of 18 gliomas. It showed that human LNX was downregulated in 100% of gliomas including low- and high-grade ones, which was confirmed by Northern blot. In situ hybridization analysis revealed that LNX was lowly expressed in cytoplasm of glioma cells. Thus, LNX might act as a diagnostic marker and a potential therapeutic target for glioma. Two-hybrid screen in yeast was used to identify human LNX interacting proteins important for LNX function. It showed that human LNX interacted with Ski interacting protein (SKIP) via PDZ domains. The co-immunoprecipitation results suggested that LNX interacted with SKIP in HEK293 cells. LNX could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch. The presence of multiple protein binding domains involved in signal transduction and interaction with Numb and SKIP suggested an important role for LNX in tumorogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Magnetic multilayers on nanospheres.

Thin-film technology is widely implemented in numerous applications. Although flat substrates are commonly used, we report on the advantages of using curved surfaces as a substrate. The curvature induces a lateral film-thickness variation that allows alteration of the properties of the deposited material. Based on this concept, a variety of implementations in materials science can be expected. As an example, a topographic pattern formed of spherical nanoparticles is combined with magnetic multilayer film deposition. Here we show that this combination leads to a new class of magnetic material with a unique combination of remarkable properties: The so-formed nanostructures are monodisperse, magnetically isolated, single-domain, and reveal a uniform magnetic anisotropy with an unexpected switching behaviour induced by their spherical shape. Furthermore, changing the deposition angle with respect to the particle ensemble allows tailoring of the orientation of the magnetic anisotropy, which results in tilted nanostructure material.

Cobalt↗

PubMed2004

Molecular cloning and characterization of a novel human BTB domain-containing gene, BTBD10, which is down-regulated in glioma.

The broad-complex, tramtrack (ttk) and bric-a-brac/poxvirus and zinc finger proteins (BTB/POZ) domain is highly conserved in a large family of eukaryotic proteins and is crucial for the latter's diverse roles in mediating interactions among proteins that are involved in transcription regulation and chromatin structures. From a fetal brain cDNA library, we isolated a cDNA of 2489 base pairs (bp) encoding a novel human BTB domain-containing protein named BTBD10. The cDNA contained an open-reading frame (ORF) of 1428 bp encoding a putative 475-amino acid (aa) protein. The BTBD10 gene was located on human chromosome 11p15.2 and consisted of nine exons spanning about 75.2 kilobase pairs (kb) of the human genome. The cDNA microarray analysis showed that BTBD10 was down-regulated in all 18 glioma samples. The expression pattern of BTBD10 gene was examined by multiple tissue cDNA (MTC) panels (Clontech), which showed a ubiquitous expression pattern in the 16 tissues examined with high expression in adult brain, testis and small intestine and weak expression in the heart, lung, liver, kidney, pancreas, spleen, thymus, prostate, ovary and colon. The subcellular localization result revealed that BTBD10 was located specifically in the nucleus of HEK293 and COS7 cell lines, suggesting that it may function in transcriptional regulation. The different expression patterns of BTBD10 in different grades of glioma versus normal brain were also examined by RT-PCR and Northern blot. We also investigated the expression of BTBD10 in hepatocellular carcinoma, ovary cancer and lung cancer, and the results revealed no significant difference in these three tumors. All these data suggested that BTBD10 might play a role in glioma.

Adolescent↗

PubMed2004

Identification and characterization of NBEAL1, a novel human neurobeachin-like 1 protein gene from fetal brain, which is up regulated in glioma.

The Beige and Chediak-Higashi (BEACH) domain is highly conserved in a large family of eukaryotic proteins, and is crucial for their functions in vesicle trafficking, membrane dynamics and receptor signaling. From a fetal brain cDNA library, we isolated a cDNA of 3858 bp encoding a novel human BEACH protein, which was named as human neurobeachin-like 1 (NBEAL1) gene. The cDNA had an open reading frame (ORF) of 3006 bp encoding a putative 1001 amino acid protein. The NBEAL1 gene was located on human chromosome 2q33-2q34 and consisted of 25 exons spanning about 73 kb of the human genome. PSORT analysis indicated that the NBEAL1 protein contained a vacuolar-targeting motif ILPK, which suggested the protein might be located in the cell lysosome. The expression pattern was examined by reverse transcription/polymerase chain reaction (RT-PCR), which showed that the transcripts were highly expressed in the human brain, kidney, prostate, and testis while lowly in the ovary, small intestine, colon and peripheral blood leukocyte. In addition, the RT-PCR result of and Northern blot showed that the novel gene was highly expressed in the biopsies of different grade glioma, especially in that of lower grade ones, which suggested it might be correlative with the glioma.

Adolescent↗

PubMed2004

Secreted brevican mRNA is expressed in the adult rat pituitary.

Brevican is the most abundant chondroitin sulfate proteoglycan in the extracellular matrix (ECM) of the adult rat brain. It has been found only in the central nervous system (CNS). In this study, we found that secreted brevican transcript was detectable in the pituitary of both male and female adult rats by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification. In posterior lobe of pituitary, pituicytes were heavily labelled. In anterior and intermediate lobes of pituitary, signals for brevican transcripts were observed in cells of various sizes. These data demonstrated that secreted brevican mRNA is expressed in the adult rat pituitary and brevican might not be a CNS-specific ECM.

Animals↗

PubMed2004

Cloning and characterization of a novel human cDNA encoding a J-domain protein (DNAJA5) from the fetal brain.

J-domain proteins are involved in protein importing and sorting, protein translocation into the endoplasmic reticulum and interaction with hsp70, cell cycle regulation and exocytosis. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone encoding a putative 531 amino acid protein with a DnaJ domain and C2H2-type zinc finger motif, which was named as DNAJA5 (human DnaJ homology subfamily A member 5). The putative protein of DNAJA5 gene was homologous to Caenorhabditis elegans DNJ-17 (identity 33.2% similarity 45.1%). By mapping, we located DNAJA5 gene to human chromosome 5p12-5p13. The DNAJA5 gene contained at least 12 exons that spanned more than 25.6 kb of the genomic sequence. The reverse transcription-polymerase chain reaction analysis indicated that it was expressed in the human brain, placenta, kidney and pancreas. DNAJA5 might play a role in co-operating with Hsp70.

Amino Acid Sequence↗

PubMed2003

Neuroprotection by the stable nitroxide 3-carbamoyl-proxyl during reperfusion in a rat model of transient focal ischemia.

OBJECT: Nitroxides mimic superoxide dismutase (SOD) biochemically and may prevent free radical oxidative injury in settings in which endogenous SOD is overwhelmed. The authors have previously shown the efficacy of a nitroxide, Tempol, in reducing stroke infarct size. Of the nitroxides, 3-carbamoyl-proxyl (3-CP) is especially promising for clinical use, because it does not cause hypotension in animals. Its efficacy in brain ischemia, however, is untested. The goal of this study was to ascertain whether 3-CP would reduce brain damage in a rat ischemia-reperfusion model. METHODS: The authors performed a blinded, dose-response study of the effect of different amounts of 3-CP (1, 10, and 100 mg/kg) on infarct size at 24 hours after focal ischemia and reperfusion. The 3-CP was given intravenously during reperfusion, which followed 1 hour of reversible ischemia induced by a thread placed intraluminally in the middle cerebral artery of rats. Brain infarcts, measured with 2,3,5-triphenyltetrazolium chloride staining in six 3-CP groups, were compared with those measured in controls (animals given an equal volume of saline). Edema-corrected infarct sizes (mean +/- standard deviation) were as follows: 146 +/- 64 mm3 in controls; 107 +/- 18 mm3 in rats given 1 mg/kg 3-CP; 40 +/- 20 mm3 in those given 10 mg/kg 3-CP; and 44 +/- 17 mm3 in those given 100 mg/kg 3-CP. A statistically significant reduction in infarct size was achieved in the 10- and 100-mg/kg 3-CP-treated groups (p < 0.01). A reduction in infarct size was also seen in the 1 mg/kg 3-CP-treated group, but this did not reach statistical significance. The authors observed no effects of 3-CP on blood pressure or brain temperature. CONCLUSIONS: Given at reperfusion, 3-CP significantly decreases brain infarct size at doses of 10 and 100 mg/kg without causing hypotension. The authors found that 3-CP is well suited for further laboratory and clinical use in brain ischemia and reperfusion.

Animals↗