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Biomedical subjects

J Q Feng

Publications and source records attributed to J Q Feng.

At least 19 recordsLinked to original sources
PubMed2006

Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.

The aim of this study was to investigate the role of JAK-STAT pathway in the cytoprotection afforded by preconditioning with H(2)O(2). It was shown that (1) Preconditioning with 100 micromol/L H(2)O(2) can markedly protect PC12 cells against apoptosis and cytotoxicity induced by 300 micromol/L H(2)O(2); (2) The expression and tyrosine phosphorylation of JAK2, not JAK1 were rapidly increased at 5 min after H(2)O(2) preconditioning; (3) The expression of STAT1 and STAT3 were significantly increased at 15 min after H(2)O(2) preconditioning, and the pTyr-STAT1 and pTyr-STAT3 were markedly increased at 60 min after H(2)O(2) preconditioning; (4) Pretreatment with the JAK inhibitor AG-490 (10 micromol/L) 20 min before H(2)O(2) preconditioning blocked not only the activation of JAK2, STAT1 and STAT3, but also the cytoprotection of H(2)O(2) preconditioning against apoptosis and cytotoxicity induced by oxidative stress. These findings suggested that preconditioning with H(2)O(2) activated the JAK-STAT pathway that played an important role in the cytoprotection induced by H(2)O(2) preconditioning.

Animals↗
PubMed2006

Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway.

The aim of present study is to explore the cytoprotection of curcumin against 1-methyl-4-phenylpridinium ions (MPP(+))-induced apoptosis and the molecular mechanisms underlying in PC12 cells. Our findings indicated that MPP(+) significantly reduced the cell viability and induced apoptosis of PC12 cells. Curcumin protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by inducing overexpression of Bcl-2, but also reducing the loss of mitochondrial membrane potential (MMP), an increase in intracellular reactive oxygen species (ROS) and overexpression of inducible nitric oxide synthase (iNOS). The selective iNOS inhibitor AG partly blocked MPP(+)-induced apoptosis of PC12 cells. The results of present study suggested that the cytoprotective effects of curcumin might be mediated, at least in part, by the Bcl-2-mitochondria-ROS-iNOS pathway. Because of its non-toxic property, curcumin could be further developed to treat the neurodegenerative diseases which are associated with oxidative stress, such as Parkinson's disease (PD).

1-Methyl-4-phenylpyridinium↗
PubMed2003

The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development.

Dentin Matrix Protein 1 (Dmp1) was originally identified from dentin. However, its expression and function in vivo are not clear. To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene. Northern blot analysis shows the expected 5.8-kb Dmp1-lacZ fusion transcript and loss of the wild-type 2.8-kb Dmp1 transcript, confirmed by a lack of immunostaining for the protein. Using heterozygous animals, we demonstrate that Dmp1 is specific for mineralized tissues. Not previously shown, Dmp1 is also expressed in pulp cells. Dmp1-deficient embryos and newborns display no apparent gross abnormal phenotype, although there are a modest expansion of the hypertrophic chondrocyte zone and a modest increase in the long bone diameter. This suggests that DMP1 is not essential for early mouse skeletal or dental development.

Animals↗
PubMed2002

Identification of cis-DNA regions controlling Bmp4 expression during tooth morphogenesis in vivo.

Epithelial-mesenchymal interactions are required for tooth formation. Bone morphogenetic protein 4 (Bmp4) is a crucial signaling molecule during this process. For better understanding of the role of the Bmp4 gene during tooth development, we studied the mechanisms that control its temporal and spatial expression during development. Using a transgenic approach, we determined that the domains which controlled Bmp4 expression in epithelium-derived ameloblasts were located in the region between 0.26 kb and 1.1 kb of the murine Bmp4 promoter. In contrast, the domains controlling Bmp4 expression in mesenchyme-derived odontoblasts and pulp cells existed in other regions of the Bmp4 gene. We have also demonstrated that the domains controlling Bmp4 expression in primordial tooth cells differ from those controlling Bmp4 expression in mature tooth tissues. The determination of unique domains by controlling the expression of the Bmp4 gene suggests that different transcriptional factors regulate the Bmp4 level at different stages during tooth morphogenesis.

Ameloblasts↗
PubMed2001

Rapid in vivo functional analysis of transgenes in mice using whole body imaging of luciferase expression.

The use of transgenic animals in biomedical research is increasing rapidly and may be the best means of determining gene function. Generating transgenic animals typically requires time-consuming screening processes, and gene function is assessed by an array of difficult phenotypic and biochemical assays performed ex vivo. To address the unmet need in transgenic research for functional assays performed with ease in living animals, we demonstrate here that in vivo detection of luciferase enzyme as a transcriptional reporter facilitates rapid screening for both the presence and function of transgenes in intact living mice. Using this approach we identified three bioluminescent transgenic founders where the transgene consisted of the heme oxygenase promoter fused to the modified coding sequence of the luciferase gene. These founders were identified from 183 pups and confirmed by PCR analysis. Identification of HO-1-luc homozygotes from back- crossed F2 littermates was then accelerated by in vivo imaging. In another transgenic mouse line, where the transgene was comprised of the bone morphogenic-4 (BMP4) promoter fused to the modified luciferase gene, we were able to identify transgenic animals and in each line we were able to visualize patterns of expression in living animals over time. The light production from these transgenic mice indicated that the desired DNA fragment was functional and different expression profiles apparent at different ages and after gene induction.

Animals↗
PubMed1998

Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages.

Cumulative evidence indicates that osteoblasts and adipocytes share a common mesenchymal precursor and that bone morphogenetic proteins (BMPs) can induce both osteoblast and adipocyte differentiation of this precursor. In the present study, we investigated the roles of BMP receptors in differentiation along these separate lineages using a well-characterized clonal cell line, 2T3, derived from the mouse calvariae. BMP-2 induced 2T3 cells to differentiate into mature osteoblasts or adipocytes depending upon culture conditions. To test the specific roles of the type IA and IB BMP receptor components, truncated and constitutively active type IA and IB BMP receptor cDNAs were stably expressed in these cells. Overexpression of truncated type IB BMP receptor (trBMPR-IB) in 2T3 cells completely blocked BMP-2-induced osteoblast differentiation and mineralized bone matrix formation. Expression of trBMPR-IB also blocked mRNA expression of the osteoblast specific transcription factor, Osf2/ Cbfa1, and the osteoblast differentiation-related genes, alkaline phosphatase (ALP) and osteocalcin (OC). BMP-2-induced ALP activity could be rescued by transfection of wild-type (wt) BMPR-IB into 2T3 clones containing trBMPR-IB. Expression of a constitutively active BMPR-IB (caBMPR-IB) induced formation of mineralized bone matrix by 2T3 cells without addition of BMP-2. In contrast, overexpression of trBMPR-IA blocked adipocyte differentiation and expression of caBMPR-IA induced adipocyte formation in 2T3 cells. Expression of the adipocyte differentiation-related genes, adipsin and PPARgamma, correlated with the distinct phenotypic changes found after overexpression of the appropriate mutant receptors. These results demonstrate that type IB and IA BMP receptors transmit different signals to bone-derived mesenchymal progenitors and play critical roles in both the specification and differentiation of osteoblasts and adipocytes.

Adipocytes↗
PubMed1998

Genomic organization, chromosomal mapping, and promoter analysis of the mouse dentin sialophosphoprotein (Dspp) gene, which codes for both dentin sialoprotein and dentin phosphoprotein.

Our laboratory has reported that two major noncollagenous dentin proteins, dentin sialoprotein and dentin phosphoprotein, are specific cleavage products of a larger precursor protein termed dentin sialophosphoprotein (MacDougall, M., Simmons, D., Luan, X., Nydegger, J., Feng, J. Q., and Gu, T. T. (1997) J. Biol. Chem. 272:835-842). To confirm our single gene hypothesis and initiate in vitro promoter studies, we have characterized the structural organization of the mouse dentin sialophosphoprotein gene. This gene has a transcription unit of approximately 9.4 kilobase pairs and is organized into 5 exons and 4 introns. Exon 1 contains a noncoding 5' sequence, and exon 2 contains the transcriptional start site, signal peptide, and first two amino acids of the NH2 terminus. Exons 3 and 4 contain coding information for 29 and 314 amino acids, respectively. The remainder of the coding information and the untranslated 3' region are contained in exon 5. Chromosomal mapping localized the gene to mouse chromosome 5q21 in close proximity to other dentin/bone matrix genes. Computer analysis of the promoter proximal 1.6-kilobase pair sequence revealed a number of potentially important cis-regulatory sequences; these include the recognition elements of AP-1, AP-2, Msx-1, serum response elements, SP-1, and TCF-1. In vitro studies showed that the DSPP promoter is active in an odontoblast cell line, MO6-G3, with basal activity mapped to -95 bp. Two potential enhancer and suppresser elements were identified in the regions between -1447 and -791 bp and -791 and -95 bp, respectively. The structural organization of the dentin sialophosphoprotein gene confirms our finding that both dentin sialoprotein and dentin phosphoprotein are encoded by a single gene with a continuous open reading frame.

Amino Acid Sequence↗
PubMed1998

[Changes of K+ channel current in cerebellar cortical neuron of apoptosis induced with H2O2].

The neurons dissociated from the cerebellar cortex of neonatal SD rat were cultured, while the growth of non-neuron cells were suppressed by Ara-c. Apoptosis of the neurons were induced with H2O2. The changes of Ik were studied during apoptosis using the patch clamp technique in cell-attached configurations. The results are as follows: (1) the Ik amplitudes of the neurons were lower than that of normal at various corresponding clamp voltages; (2) the conductances, mean open time, open probability, long and short opening time constants were all lower, as compared with normal neurons. All these results indicate that the activities of K+ channels on cerebellar neurons decrease during apoptosis.

Animals↗
PubMed1997

Propofol potentiates the depressant effect of alfentanil in isolated neonatal rat spinal cord and blocks naloxone-precipitated hyperresponsiveness.

Our previous studies have shown that a benzodiazepine potentiates opioid actions on spinal cord by blocking a hyperresponsiveness that may be related to the development of opioid tolerance and withdrawal. The present study was designed to test whether propofol, which like benzodiazepines acts on GABA(A) receptors, displays similar interactions with opioids. Spinal cords isolated from 1-7 day old rats were arranged to record the slow ventral root potential (sVRP) elicited by stimulating a lumbar dorsal root. A concentration of propofol which by itself did not depress sVRP significantly enhanced the apparent potency of alfentanil and blocked the increase in sVRP observed when alfentanil is followed by naloxone. The results suggest that enhancement of GABA inhibition may increase opioid potency by inhibiting the development of acute tolerance.

Alfentanil↗
PubMed1997

Bone morphogenetic protein 2 transcripts in rapidly developing deer antler tissue contain an extended 5' non-coding region arising from a distal promoter.

To understand the regulation of the BMP-2 gene expression, we recently isolated the BMP-2 gene from a mouse genomic library and characterized the exon-intron structure and promoter. RNase protection assay using poly (A)+ RNA of mouse osteoblasts demonstrates that two regions in BMP-2 gene are protected by antisense mouse BMP-2 RNA probes. These results demonstrate that BMP-2 gene utilizes two alternative promoters, a distal and a proximal promoter. In the present study we demonstrate that BMP-2 mRNA from rapidly growing deer antler tissue has an extended 5' non-coding region compared with the human and rat BMP-2 mRNA. The extended 5' non-coding region in the deer mRNA represents transcripts from the upstream distal promoter. This is the first evidence of a natural BMP-2 mRNA from a bone-forming tissue that most likely initiated from the distal transcription start site.

Alternative Splicing↗
PubMed1997

Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts.

Normal bone formation is a prolonged process that is carefully regulated and involves sequential expression of growth regulatory factors by osteoblasts as they proliferate and ultimately differentiate. Since this orderly sequence of gene expression by osteoblasts suggests a cascade effect, and BMP-2 is capable of initiating and maintaining this effect, we examined the effects of BMP-2 on expression of other BMPs and compared these effects with the expression pattern of bone cell differentiation marker genes in primary cultures of fetal rat calvarial (FRC) osteoblasts. To examine the gene expression profile during bone cell differentiation and bone formation, we also examined the effects of rBMP-2 on bone formation in vivo and in vitro. rBMP-2 stimulated bone formation on the periosteal surface of mice when 500 ng/day rBMP-2 was injected subctaneously. When rBMP-2 was added to primary cultures of FRC osteoblasts, it accelerated mineralized nodule formation in a time and concentration-dependent manner (10-40 ng/ml). rBMP-2 (40 ng/ml) enhanced BMP-3 and -4 mRNA expression during the mineralization phase of primary cultures of FRC osteoblasts. Enhancement of BMP-3 and -4 mRNA expression by rBMP-2 was associated with increased expression of bone cell differentiation marker genes, alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), osteopontin (OP), and bone sialoprotein (BSP). These results suggest that BMP-2 enhances expression of other BMP genes during bone cell differentiation. BMP-2 may act in a paracrine fashion in concert with other BMPs it induces to stimulate bone cell differentiation and bone formation during remodeling.

Amino Acid Sequence↗
PubMed1997

[Effect of pregnenolone sulfate on delayed rectifier K+ channel in pyramidial neuron of cerebral cortex].

Recent studies have shown that endogenous brain metabolites of steroids may exert important nongenomic modulatory effects on neuronal mechanisms. In this work the effect of pregnenolone sulfate (PS) on delayed rectifier K+ channel (IK) was studied in acutely dissociated rat cerebral cortical pyramidial neurons by means of cell-attached and inside-out patch clamp techniques. The open probability and mean open time of the IK channels were increased by PS in a concentration-dependent manner over the range of 30-100 mumol/L. but without changing the IK amplitude.

Animals↗
PubMed1995

The mouse bone morphogenetic protein-4 gene. Analysis of promoter utilization in fetal rat calvarial osteoblasts and regulation by COUP-TFI orphan receptor.

Bone morphogenetic protein-4 (BMP-4) is one of a member of related polypeptides that are important in bone formation and other developmental processes. We isolated the BMP-4 gene from a mouse genomic library and characterized the exon-intron structure and one of the candidate promoters. Two alternative 5'-noncoding exons, 1A and 1B, were identified by reverse transcription polymerase chain reaction assays. Quantitative competitive polymerase chain reaction using Exon 1A, Exon 1B, and Exon 3 primers indicate the 1A-containing transcript is the primary BMP-4 mRNA expressed in bone cell cultures. Primer extension analysis supports that 1A is the major promoter utilized in bone cell cultures as well as in 9.5-day mouse embryos. 1A promoter activity indicate selective DNA regions functional in bone cells. We found potential regulatory response regions in the 1A 5'-flanking region of the BMP-4 gene for the chicken ovalbumin upstream-transcription factor I (COUP-TFI). Specific binding to the COUP-TFI response regions in the BMP-4 1A promoter was demonstrated. By co-transfection of a COUP-TFI expression plasmid with the BMP-4 1A promoter in fetal rat calvarial osteoblasts, we demonstrated that COUP-TFI inhibits the BMP-4 promoter activity. This suggests that COUP-TFI could act as a silencer for BMP-4 transcription in vivo.

Amino Acid Sequence↗
PubMed1995

Deer antler tissue contains two types of bone morphogenetic protein 4 mRNA transcripts.

Previously we isolated a bone morphogenetic protein 4 (BMP-4) cDNA from human prostate cancer cells and found that the 5' noncoding exon 1 of this BMP-4 cDNA was different from that of human bone cell BMP-4 cDNA. Recently we identified two alternate exon 1s, 1A and 1B, for BMP-4 gene by reverse transcription-polymerase chain reaction (RT-PCR) assays from fetal rat calvarial osteoblasts. In order to further examine alternate exon 1 usage in the BMP-4 gene, we screened deer antler tissue cDNA library. We isolated two types of cDNA clones encoding BMP-4 from this deer antler cDNA library. Sequencing of these clones have revealed a single open reading frame encoding a 408 amino acid protein. Comparison of 5' noncoding exon 1 portion of these cDNA sequences with those of human bone and prostate BMP-4 cDNA sequences and mouse BMP-4 genomic DNA sequence demonstrated that deer antler tissue expresses both exon 1A and 1B containing BMP-4 mRNA transcripts. This suggests that BMP-4 gene may contain alternate promoters or alternate splicing sites in deer antler tissue.

Amino Acid Sequence↗
PubMed1995

Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells.

We have examined expression of bone morphogenetic protein 3 (BMP-3) mRNA in normal rat osteoblasts in culture as they undergo differentiation to form bone-like structures, and have found that expression of BMP-3 mRNA in primary fetal rat calvarial (FRC) cells is discontinuous and shows at least four different-sized transcripts. BMP-3 mRNA expression has a distinct temporal pattern during bone cell differentiation of FRC osteoblasts. Previously, we showed that BMP-3 mRNA is expressed in normal and neoplastic rat and human prostate tissues, and in human osteosarcoma cells, as multiple transcripts. To compare the nature of these transcripts in different tissues, three cDNA clones encoding BMP-3 have been isolated by reverse transcription-polymerase chain reaction (RT-PCR) and cDNA library screening from human prostate cancer PC-3 cells, rat prostate adenocarcinoma PA III cells, and primary FRC cells. Analysis of these clones has revealed that the nucleotide sequence of BMP-3 found in human prostate cells is identical to that found in human bone cells. The rat BMP-3 sequences from bone and prostate cells are also identical but show a high degree of variation in the pro- or precursor region compared with human BMP-3. The biological significance of these differences in these two species is unknown.

Adenocarcinoma↗
PubMed1994

Structure and sequence of mouse bone morphogenetic protein-2 gene (BMP-2): comparison of the structures and promoter regions of BMP-2 and BMP-4 genes.

Screening of a mouse spleen genomic DNA library with mouse BMP-4 and BMP-2 cDNA probes led to the isolation of mouse BMP-2 gene. This gene contains approximately 11 kb transcription unit and 3 exons. The deduced protein has 394 amino acids. The C-terminal amino acid mature coding region is identical to that of the human BMP-2. Comparison of mouse BMP-2 and BMP-4 gene shows little similarity in exon/intron structure, although the mature coding peptide regions of both genes share over 90% identity at the amino acid level.

Amino Acid Sequence↗