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Zhiping Li

Publications and source records attributed to Zhiping Li.

At least 37 records · Page 2Linked to original sources
PubMed2005

CuBr-catalyzed direct indolation of tetrahydroisoquinolines via cross-dehydrogenative coupling between sp3 C-H and sp2 C-H bonds.

A novel and efficient C-C bond formation method was developed via the cross-dehydrogenative coupling (CDC) reaction of indoles and tetrahydroisoquinolines catalyzed by copper bromide in the presence of an oxidizing reagent, tert-BuOOH. The CDC reaction provides a simple and efficient catalytic method to construct indolyl tetrahydroisoquinolines via a combination of sp3 C-H bond and sp2 C-H bond followed by C-C bond formation.

Journal Article↗
PubMed2005

Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment.

The cyclin D1 gene encodes the labile serum-inducible regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. Overexpression of cyclin D1 promotes cellular proliferation and normal physiological levels of cyclin D1 function to inhibit adipocyte differentiation in vivo. We have previously shown that cyclin D1 inhibits peroxisome proliferator-activated receptor (PPAR)gamma-dependent activity through a cyclin-dependent kinase- and retinoblastoma protein-binding-independent mechanism. In this study, we determined the molecular mechanism by which cyclin D1 regulated PPARgamma function. Herein, murine embryonic fibroblast (MEF) differentiation by PPARgamma ligand was associated with a reduction in histone deacetylase (HDAC1) activity. Cyclin D1-/- MEFs showed an increased propensity to undergo differentiation into adipocytes. Genetic deletion of cyclin D1 reduced HDAC1 activity. Reconstitution of cyclin D1 into the cyclin D1-/- MEFs increased HDAC1 activity and blocked PPARgamma-mediated adipogenesis. PPARgamma activity was enhanced in cyclin D1-/- cells. Reintroduction of cyclin D1 inhibited basal and ligand-induced PPARgamma activity and enhanced HDAC repression of PPARgamma activity. Cyclin D1 bound HDAC in vivo and preferentially physically associated with HDAC1, HDAC2, HDAC3, and HDAC5. Chromatin immunoprecipitation assay demonstrated that cyclin D1 enhanced recruitment of HDAC1 and HDAC3 and histone methyltransferase SUV39H1 to the PPAR response element of the lipoprotein lipase promoter and decreased acetylation of total histone H3 and histone H3 lysine 9. Collectively, these studies suggest an important role of cyclin D1 in regulation of PPARgamma-mediated adipocyte differentiation through recruitment of HDACs to regulate PPAR response element local chromatin structure and PPARgamma function.

3T3 Cells↗
PubMed2005

BCL-6 negatively regulates expression of the NF-kappaB1 p105/p50 subunit.

BCL-6 is a transcription repressor frequently deregulated in non-Hodgkin's B cell lymphomas. Its activity is also critical to germinal center development and balanced Th1/Th2 differentiation. Previous studies have suggested that NF-kappaB activity is suppressed in germinal center and lymphoma B cells that express high levels of BCL-6, and yet the reason for this is unknown. We report in this study that BCL-6 can bind to three sequence motifs in the 5' regulatory region of NF-kappaB1 in vitro and in vivo, and repress NF-kappaB1 transcription both in reporter assays and in lymphoma B cell lines. BCL-6(-/-) mice further confirm the biological relevance of BCL-6-dependent regulation of NF-kappaB1 because BCL-6 inactivation caused notable increase in p105/p50 proteins in several cell types. Among these, BCL-6(-/-) macrophage cell lines displayed a hyperproliferation phenotype that can be reversed by NF-kappaB inhibitors, e.g., N-tosyl-l-phenylalanine chloromethyl ketone and SN50, a result that is consistent with increased nuclear kappaB-binding activity of p50 homodimer and p50/p65 heterodimer. Our results demonstrate that BCL-6 can negatively regulate NF-kappaB1 expression, thereby inhibiting NF-kappaB-mediated cellular functions.

Animals↗
PubMed2005

Cytochrome P450 gene polymorphisms and risk of low birth weight.

This study investigated the association between polymorphisms in cytochrome P450 genes (CYP1A1MspI, CYP1A1HincII, and CYP2E1) and low birth weight. Between July 1999 and June 2002, we conducted a study using infant-parents triads in Anqing, China. The analyses included the families of 248 normal birth weight, full-term infants, and 248 low-birth-weight infants. Genotyping was performed for the polymorphisms of cytochrome P450 genes using standard techniques. We used log-linear modeling to analyze the association of CYP1A1 and CYP2E1 gene polymorphisms with the risk of low birth weight. In the analysis of children's genotypes, the relative risk was 1.92 (95% confidence interval: 1.05, 3.52, p=0.034) for CYP1A1MspI C/C6235 compared with CYP1A1 MspI T/T6235. In the analysis of mothers' genotypes, an association was also seen for maternal CYP1A1MspI C/C6235 compared with CYP1A1MspI T/T6235 (relative risk: 1.68, 95% confidence interval: 1.06, 2.68, p=0.029). We did not observe a joint effect between mother's and children's genotypes. Analysis of control triads suggests Mendelian transmissions of the variant alleles of CYP1A1MspI, CYP1A1HincII, and CYP2E1. In conclusion, both infant and maternal CYP1A1MspI C/C6235 genotypes were associated with increased risk of low birth weight in our study population. This suggests a possible role for human cytochrome P450 variability in the etiology of low birth weight.

Alleles↗
PubMed2005

Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease.

Dietary factors promote obesity and obesity-related disorders, such as fatty liver disease. Natural killer T (NKT) cells are components of the innate immune system that regulate proinflammatory (Th-1) and anti-inflammatory (Th-2) immune responses. Previously, we noted that NKT cells are selectively reduced in the fatty livers of obese, leptin-deficient ob/ob mice and demonstrated that this promotes proinflammatory polarization of hepatic cytokine production, exacerbating lipopolysaccharide (LPS) liver injury in these animals. In the current study, we show that hepatic NKT cells are also depleted by diets that induce obesity and fatty livers in wild-type mice, promoting Th-1 polarization of hepatic cytokine production and sensitization to LPS liver injury despite persistent leptin. Adult male C57BL6 mice fed diets containing high amounts of either fat or sucrose, or combined high-fat, high-sucrose, develop increased hepatic NKT cell apoptosis and reduced liver NKT cells. The hepatic lymphocytes are more Th-1 polarized with increased intracellular interferon gamma and tumor necrosis factor alpha. Mice fed high-fat diets also exhibit more liver injury, reflected by 2-fold greater serum alanine aminotransferase (ALT) than control animals after receiving LPS. In conclusion, when otherwise normal mice are fed with high-fat or sucrose diet, they become obese, develop fatty livers, and acquire hepatic innate immune system abnormalities, including increased NKT cell apoptosis. The latter reduces liver NKT cell populations and promotes excessive hepatic production of Th-1 cytokines that promote hepatic inflammation. These diet-induced alterations in the hepatic innate immune system may contribute to obesity-related liver disease.

Animals↗
PubMed2005

Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects.

BACKGROUND: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha1A-adrenergic receptor (alpha1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level. METHODS: A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. RESULTS: BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha1A-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours. CONCLUSION: Our data suggest that the alpha1A-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha1A-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.

Aged↗
PubMed2004

Synthesis of 1,1,4,4-tetrabromo-2-butenes and related compounds via desilylation-bromination of silylated 1,3-butadiene derivatives.

The combination of zirconocene-mediated coupling of silylated alkynes with a protonation-desilylation or bromination-desilylation process afforded otherwise unavailable butadiene derivatives. When (E,E)-2,3-dialkyl-1,4-bis(trimethylsilyl)-1,3-butadienes were treated with 3 equiv of Br(2) in CH(2)Cl(2), (E)-2,3-dialkyl-1,1,4,4-tetrabromo-2-butenes were obtained in excellent yields with perfect stereoselectivity.

Journal Article↗
PubMed2004

Minireview: Cyclin D1: normal and abnormal functions.

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein and promotes progression through the G1-S phase of the cell cycle. Amplification or overexpression of cyclin D1 plays pivotal roles in the development of a subset of human cancers including parathyroid adenoma, breast cancer, colon cancer, lymphoma, melanoma, and prostate cancer. Of the three D-type cyclins, each of which binds cyclin-dependent kinase (CDK), it is cyclin D1 overexpression that is predominantly associated with human tumorigenesis and cellular metastases. In recent years accumulating evidence suggests that in addition to its original description as a CDK-dependent regulator of the cell cycle, cyclin D1 also conveys cell cycle or CDK-independent functions. Cyclin D1 associates with, and regulates activity of, transcription factors, coactivators and corepressors that govern histone acetylation and chromatin remodeling proteins. The recent findings that cyclin D1 regulates cellular metabolism, fat cell differentiation and cellular migration have refocused attention on novel functions of cyclin D1 and their possible role in tumorigenesis. In this review, both the classic and novel functions of cyclin D1 are discussed with emphasis on the CDK-independent functions of cyclin D1.

Animals↗
PubMed2004

Novel synthetic route to octasubstituted naphthalenes from four alkynes and one olefin unit via zirconacyclopentadienes and 1,2-diiodo-3,4,5,6-tetraalkylbenzene.

1,2,3,4-Tetrasubstituted benzene derivatives were prepared by the reaction of zirconacyclopentadienes with vinyl bromide in the presence of NiCl(2)(PPh(3))(2). 1,2-Diiodo-3,4,5,6-tetraalkylbenzenes were formed by treatment of 1,2,3,4-tetraalkylbenzenes with iodine and periodic acid in the presence of a catalytic amount of sulfuric acid. Reaction of the 1,2-diiodo-3,4,5,6-tetraalkylbenzenes with zirconacyclopentadienes in the presence of a stoichiometric amount of CuCl gave sterically crowded octasubstituted naphthalenes in moderate yields.

Journal Article↗
PubMed2004

Zirconocene-mediated intermolecular coupling of one molecule of Si-tethered diyne with three molecules of organonitriles: one-pot formation of pyrrolo[3,2-c]pyridine derivatives via cleavage of CN triple bonds of organonitriles.

One Si-tethered diyne is coupled in one pot with three molecules of organonitriles promoted by a low-valent zirconocene species. Cleavage of one of the three CN triple bonds and cleavage of the two Si-C bonds take place to afford pyrrolo[3,2-c]pyridine derivatives after hydrolysis.

Journal Article↗
PubMed2004

Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis.

It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of ob/ob mice promotes depletion of liver NKT cells, thereby sensitizing ob/ob livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic NKT cells were quantified in wild-type mice before and after treatment with NE inhibitors, and in dopamine beta-hydroxylase knockout mice (which cannot synthesize NE) and ob/ob mice before and after 4 weeks of NE supplementation. Decreasing NE activity consistently reduces liver NKT cells, while increasing NE has the opposite effect. Analysis of hepatic and thymic NKT cells in mice of different ages demonstrate an age-related accumulation of hepatic NKT cells in normal mice, while liver NKT cells become depleted after birth in ob/ob mice, which have increased apoptosis of hepatic NKT cells. NE treatment inhibits apoptosis and restores hepatic NKT cells. In ob/ob mice with reduced hepatic NKT cells, hepatic T and NKT cells produce excessive T helper (Th)-1 proinflammatory cytokines and the liver is sensitized to LPS toxicity. NE treatment decreases Th-1 cytokines, increases production of Th-2 cytokines, and reduces hepatotoxicity. Studies of CD1d-deficient mice, which lack the receptor required for NKT cell development, demonstrate that they are also unusually sensitive to LPS hepatotoxicity. In conclusion, low NE activity increases hepatic NKT cell apoptosis and depletes liver NKT cells, promoting proinflammatory polarization of hepatic cytokine production that sensitizes the liver to LPS toxicity.

Animals↗
PubMed2004

Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice.

Constitutive beta-catenin/Tcf activity, the primary transforming events in colorectal carcinoma, occurs through induction of the Wnt pathway or APC gene mutations that cause familial adenomatous polyposis. Mice carrying Apc mutations in their germ line (ApcMin) develop intestinal adenomas. Here, the crossing of ApcMin with cyclin D1-/- mice reduced the intestinal tumor number in animals genetically heterozygous or nullizygous for cyclin D1. Decreased tumor number in the duodenum, intestines, and colons of ApcMin/cyclin D1+/- mice correlated with reduced cellular proliferation and increased differentiation. Cyclin D1 deficiency reduced DNA synthesis and induced differentiation of colonic epithelial cells harboring mutant APC but not wild-type APC cells in vivo. In previous studies, the complete loss of cyclin D1 through homozygous genetic deletion conveyed breast tumor resistance. The protection of mice, genetically predisposed to intestinal tumorigenesis, through cyclin D1 heterozygosity suggests that modalities that reduce cyclin D1 abundance could provide chemoprotection.

Adenomatous Polyposis Coli Protein↗
PubMed2003

Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice.

Leptin's actions on certain cells require a leptin-inducible neurotransmitter, norepinephrine (NE). NE modulates hepatic fibrosis. Therefore, decreased NE may explain why leptin deficiency inhibits hepatic fibrosis. We manipulated adrenergic activity in leptin-deficient ob/ob mice, leptin-sufficient, dopamine beta-hydroxylase deficient (Dbh(-/-)) mice, and HSC cultures to determine if leptin requires NE to activate HSC and induce hepatic fibrosis. ob/ob mice have chronic liver injury, but reduced numbers of HSC. Supplemental leptin increases HSC, suggesting that leptin-dependent, injury-related factors permit expansion of HSC populations. NE also increases HSC numbers and activation, normalizing fibrogenesis. When fed hepatotoxic diets, NE-deficient Dbh(-/-) mice fail to accumulate activated HSC and have impaired fibrogenesis unless treated with adrenergic agonists. NE acts directly on HSC to modulate leptin's actions because leptin increases HSC proliferation and prazosin, an alpha-adrenoceptor antagonist, inhibits this. Thus, leptin permits injury-related increases in adrenergic activity and requires NE to activate HSC and induce hepatic fibrogenesis.

Adrenergic Agonists↗
PubMed2003

Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.

Ob/ob mice, a model for nonalcoholic fatty liver disease (NAFLD), develop intestinal bacterial overgrowth and overexpress tumor necrosis factor alpha (TNF-alpha). In animal models for alcoholic fatty liver disease (AFLD), decontaminating the intestine or inhibiting TNF-alpha improves AFLD. Because AFLD and NAFLD may have a similar pathogenesis, treatment with a probiotic (to modify the intestinal flora) or anti-TNF antibodies (to inhibit TNF-alpha activity) may improve NAFLD in ob/ob mice. To evaluate this hypothesis, 48 ob/ob mice were given either a high-fat diet alone (ob/ob controls) or the same diet + VSL#3 probiotic or anti-TNF antibodies for 4 weeks. Twelve lean littermates fed a high-fat diet served as controls. Treatment with VSL#3 or anti-TNF antibodies improved liver histology, reduced hepatic total fatty acid content, and decreased serum alanine aminotransferase (ALT) levels. These benefits were associated with decreased hepatic expression of TNF-alpha messenger RNA (mRNA) in mice treated with anti-TNF antibodies but not in mice treated with VSL#3. Nevertheless, both treatments reduced activity of Jun N-terminal kinase (JNK), a TNF-regulated kinase that promotes insulin resistance, and decreased the DNA binding activity of nuclear factor kappaB (NF-kappaB), the target of IKKbeta, another TNF-regulated enzyme that causes insulin resistance. Consistent with treatment-related improvements in hepatic insulin resistance, fatty acid beta-oxidation and uncoupling protein (UCP)-2 expression decreased after treatment with VSL#3 or anti-TNF antibodies. In conclusion, these results support the concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD and suggest novel therapies for these common conditions.

Alanine Transaminase↗