Biomedical subjects

Hu Zeng

Publications and source records attributed to Hu Zeng.

8 recordsLinked to original sources

PubMed2007

B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells.

The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the functions of the AgRs in T and B cells. In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of FcepsilonR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcepsilonR-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient mast cells have normal FcepsilonR-mediated Ca(2+) flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcepsilonR-mediated activation of NF-kappaB and decreased activation of AP-1. Thus, Bcl10 is essential for FcepsilonR-induced activation of AP-1, NF-kappaB, degranulation, and cytokine production in mast cells.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.

G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-kappaB activation, the molecular mechanism by which GPCRs induced NF-kappaB activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-kappaB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid cells remains to be determined. In this study, we demonstrated that the deficiency of Bcl10 resulted in the defect in NF-kappaB activation induced by either expressing the constitutively active mutant of G protein or stimulation of cells with lysophosphatidic acid or endothelin-1, which activate their GPCR. In contrast, TNF-alpha-, LPS-, and integrin-induced NF-kappaB activation was not affected in Bcl10-deficient cells. Together, our results provide genetic evidence showing that Bcl10 is a key signaling component mediating NF-kappaB activation induced by GPCRs in nonlymphoid cells.

Adaptor Proteins, Signal Transducing↗

PubMed2006

The expression of CD9 in the peri-implantation mouse uterus is upregulated in an ovarian steroid hormone-dependent manner.

OBJECTIVE: To examine the spatiotemporal expression of CD9 protein in the peri-implantation mouse uterus as well as the effects of ovarian steroid hormones on CD9. DESIGN: Experimental animal study. SETTING: Reproductive biological center of Chinese Academy of Sciences. ANIMAL(S): Female Kunming white strain mice (6-8 weeks old). INTERVENTION(S): Subcutaneous injection of P(4)/E(2); uterine tissues were collected at different times after injection. MAIN OUTCOME MEASURE(S): The levels of protein and mRNA were detected in mouse uterus during peri-implantation and after steroid hormones treatment. RESULT(S): CD9 protein was expressed intensely in the stromal cells on days 1 and 2 of pregnancy. On days 3 and 4, the glandular and luminal epithelial cells exhibited accumulation of CD9 protein. After the initial attachment reaction on day 5, luminal epithelial and stromal cells immediately surrounding the blastocysts exhibited distinct accumulation of CD9. On days 6-8, the accumulation of CD9 occurred in decidual cells. Using ovariectomized mice, we also observed that both progesterone and estrogen upregulated uterine CD9 expression. CONCLUSION(S): The results of the current investigation showed that CD9 was differentially expressed in the uterus depending on the stage of implantation and was upregulated in ovarian steroid hormone-dependent manner, implicating multiple roles of CD9 in the regulation of embryo implantation during the peri-implantation period.

Animals↗

PubMed2006

Essential role of phospholipase C gamma 2 in early B-cell development and Myc-mediated lymphomagenesis.

Phospholipase Cgamma2 (PLCgamma2) is a critical signaling effector of the B-cell receptor (BCR). Here we show that PLCgamma2 deficiency impedes early B-cell development, resulting in an increase of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B cells. PLCgamma2 deficiency impairs pre-BCR-mediated functions, leading to enhanced interleukin-7 (IL-7) signaling and elevated levels of RAGs in the selected large pre-B cells. Consequently, PLCgamma2 deficiency renders large pre-B cells susceptible to transformation, resulting in dramatic acceleration of Myc-induced lymphomagenesis. PLCgamma2(-/-) Emu-Myc transgenic mice mainly develop lymphomas of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B-cell origin, which are uncommon in wild-type Emu-Myc transgenics. Furthermore, lymphomas from PLCgamma2(-/-) Emu-Myc transgenic mice exhibited a loss of p27Kip1 and often displayed alterations in Arf or p53. Thus, PLCgamma2 plays an important role in pre-BCR-mediated early B-cell development, and its deficiency leads to markedly increased pools of the most at-risk large pre-B cells, which display hyperresponsiveness to IL-7 and express high levels of RAGs, making them prone to secondary mutations and Myc-induced malignancy.

Animals↗

PubMed2006

Alternative 3' UTR polyadenylation of Bzw1 transcripts display differential translation efficiency and tissue-specific expression.

BZW1 is a conserved regulatory factor for transcriptional control of histone H4 gene at the G1/S transition. In this study, three Bzw1 transcripts were identified in mice with two long forms (approximately 2.9 kb) expressed ubiquitously at low level, and a short transcript of 1.8 kb expressed at high level exclusively in testis. These different transcripts share the same 5' UTR and coding sequence, but differ in the length of 3' UTR by utilizing alternative polyadenylation sites. Different translation efficiencies were observed in the cells transfected with chimeric EGFP-Bzw1 genes tailed with different 3' UTRs. Our results demonstrate that Bzw1 transcripts are alternatively polyadenylated and expressed in tissue-specific pattern.

3' Untranslated Regions↗

PubMed2004

Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells.

Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was up-regulated in human liver carcinoma compared with normal liver. PRL-3 was also highly expressed in metastatic melanoma B16-BL6 cells but not in its lowly metastatic parental cell line, B16 cells. B16 cells transfected with PRL-3 cDNA displayed morphological transformation from epithelial-like shape to fibroblast-like shape. PRL-3-overexpressed cells showed much higher migratory ability, which could be reversed by specific anti-sense oligodeoxynucleotide and the phosphatase inhibitors sodium orthovanadate or potassium bisperoxo oxovanadate V. Meanwhile, the expression of the catalytically inactive PRL-3 mutations (D72A or C104S) significantly reduced the cell migratory capability. In addition, PRL-3 transfectants demonstrated altered extracellular matrix adhesive property and up-regulated integrin-mediated cell spreading efficiency. Furthermore, we confirmed that PRL-3 could facilitate lung and liver metastasis of B16 cells in an experimental metastasis model in mice, consistent with accelerated proliferation and growth rate both in vitro and in vivo. Together, these observations provide convincing evidence that PRL-3 truly plays a causal role in tumor metastasis.

Animals↗

PubMed2004

Atomic force microscopy studies on DNA structural changes induced by vincristine sulfate and aspirin.

We report that atomic force microscopy (AFM) studies on structural variations of a linear plasmid DNA interact with various concentrations of vincristine sulfate and aspirin. The different binding images show that vincrinstine sulfate binding DNA chains caused some loops and cleavages of the DNA fragments, whereas aspirin interaction caused the width changes and conformational transition of the DNA fragments. Two different DNA structural alternations could be explained by the different mechanisms of the interactions with these two components. Our work indicates that the AFM is a powerful tool in studying the interaction between DNA and small molecules.

Aspirin↗

PubMedDate not supplied

Quantitative analysis of EcoR1 methylase-DNA complex by atomic force microscopy.

The EcoR1 methylase specifically recognize 5'-GA* ATTC-3' in DNA duplex. We directly applied atomic force microscopy (AFM) to investigate linear pBR322-EcoR1 methylase complexes and quantitatively analyzed the bend angles of linear pBR322-EcoR1 methylase complexes and the bound protein widths. In this study, we made a novel observation that DNA-EcoR1 methylase complexes exhibited two populations of conformation at recognition site: DNA bent an acute angle at the recognition site in the presence of one EcoR1 methylase monomeric molecule, while DNA bent an unacute angle at the recognition site and the complementary site on duplex DNAs in the presence of EcoR1 methylase dimer. The data indicated that the unacute angle state was the result of unique interactions between EcoR1 methylase and the recognition site and the complementary site on duplex DNAs, and suggested that the acute angle conformation could be an intermediate in the formation of the unacute angle state. Our works provide a detail insight into the DNA structural variations involved in EcoR1 methylase-binding processes and demonstrate further the versatility of AFM as an imaging technique for studying the interaction between large DNA fragment and protein.

Binding Sites↗