Abstract:
:Oleanolic acid (OA) is a natural triperpenoid that protects against a variety of hepatotoxicants such as carbon tetrachloride, cadmium, acetaminophen, and bromobenzene. To gain insight into the molecular mechanisms of this generalized hepatoprotection, genomic analysis was performed on mouse and rat livers after OA treatment. Mice and rats were given OA at a hepatoprotective dose (50 micromol/kg, s.c., daily for 4 days) and hepatic RNA was isolated, purified, and subjected to gene expression analysis. OA treatment produced changes in 5% of the genes on custom-designed mouse liver array and rat toxicology-II array. Changes in key gene expressions were further analyzed by real-time RT-PCR. OA treatment dramatically increased expression of hepatic metallothionein (Mt), and increased the expression of the nuclear factor E2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase-1 (Hmox1), and glutamate-cysteine ligases (Gclc and Gclm). OA treatment also increased the expression of genes related to cell proliferation and suppressed the expression of several cytochrome P450 genes possibly to switch cellular metabolic energy to an acute-phase response. Hepatic MT protein was increased 60- and 15-fold in mice and rats, respectively, together with a 30% increase in mouse liver zinc. These gene expression changes, particularly the dramatic induction of MT and the Nrf2 signaling, occur with hepatoprotection doses of OA, and likely are important in the generalized protective effects of OA against hepatotoxicants.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Liu J,Wu Q,Lu YF,Pi Jdoi
10.1016/j.bcp.2008.07.021subject
Has Abstractpub_date
2008-10-01 00:00:00pages
922-8issue
7eissn
0006-2952issn
1873-2968pii
S0006-2952(08)00509-1journal_volume
76pub_type
杂志文章abstract::Despite the substantial progress made in understanding initiation expression of the MOR gene in lymphocytes, the signal pathway associated with MOR gene transcription remains to be better defined. As the phosphatidylinositol 3-kinase (PI3K)/AKT pathway can mediate diverse biological responses and is crucial for optima...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.09.013
更新日期:2010-02-01 00:00:00
abstract::Exposure to ultraviolet B (UVB) irradiation induces acute skin inflammation such as erythema (sunburn) and edema, and prostaglandin (PG)E2 in the epidermis plays an important role as its prominent mediator. In the present study, we investigated the effect of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) from Citrus de...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.04.006
更新日期:2004-08-01 00:00:00
abstract::The effects of thromboxane A2 (TXA2) on the proliferation of vascular smooth muscles cells (VSMC) were examined using primary cultures of VSMC from rat aorta. U46619, a stable TXA2 mimetic, stimulated DNA synthesis of VSMC only in the presence of insulin. The effect was concentration-dependent with a half-maximal effe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90096-4
更新日期:1990-12-01 00:00:00
abstract::The carrier protein for methotrexate and tetrahydrofolate cofactors (GP-MTX) in CCRF-CEM human lymphoblastic leukemia cells in a 117 kDa glycoprotein containing both N- and O-linked oligosaccharides (Matherly et al., J Biol Chem 267: 23253-23260, 1992). Tunicamycin, an inhibitor of N-glycosylation, was used to investi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90423-5
更新日期:1994-03-15 00:00:00
abstract::On the basis of previous electrophysiological studies, it has been proposed that there are three main classes of excitatory amino acid receptor in the mammalian central nervous system, which are activated preferentially by kainic acid, quisqualic acid and N-methyl-D-aspartate respectively. Although the pharmacology of...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90213-3
更新日期:1986-02-01 00:00:00
abstract::Eighteen linear analogues of [Arg8]vasopressin (AVP) were synthesized by systematically substituting the cysteine residues at positions 1 and 6 with a range of L-amino acids. Screening by competition ligand binding revealed that the combinations of amino acid residues tolerated at these positions was very restricted w...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90523-1
更新日期:1994-04-29 00:00:00
abstract::Sublines of K562 human leukemia cells were selected for resistance (30- to 80-fold) to etoposide by continuous exposure to 0.5 microM VP-16. Two etoposide-resistant cell lines, K/VP.5 and K/VP.5-1, showed a 5-fold reduction in levels of topoisomerase II alpha protein compared with K562 cells. Northern analysis indicat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90643-b
更新日期:1993-12-03 00:00:00
abstract::The relationship between cytotoxicity and fluoropyrimidine effects on the production of mature cytoplasmic 28S and 18S ribosomal RNA was studied in S-180 cells for the fluoropyrimidines: 5-fluorouracil (FUra), 5-fluorouridine (FUrd), 5-fluorodeoxyuridine (FdUrd), and 5'-deoxy-5-fluorouridine (5'-dFUrd). After a 6-hr d...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90640-x
更新日期:1987-10-01 00:00:00
abstract::[[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)-NH(2))(2))](4+) (BBR3464) is a cationic trinuclear platinum drug that is being evaluated in phase II clinical trials for treatment of lung and ovarian cancers. The structure and DNA binding profile of BBR3464 is different from drugs commonly used clinica...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.12.016
更新日期:2007-05-01 00:00:00
abstract::Aequorin-based assays for stable fly, Stomoxys calcitrans, (STKR) and human (neurokinin receptor 1 (NK1), neurokinin receptor 2 (NK2)) neurokinin-like receptors were employed to investigate the impact of a C-terminal amino acid exchange in synthetic vertebrate ('FXGLMa') and invertebrate ('FX1GX2Ra') tachykinin-like p...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)00914-0
更新日期:2002-05-01 00:00:00
abstract::Wild-type and repair-deficient cell lines ( EM9 ) of Chinese Hamster Ovary cells were utilized to assess cytotoxic responses towards metals that produce lesions in DNA. Alkaline elution studies indicated that both CaCrO4 and HgCl2 induced single-strand breaks in the DNA. CaCrO4 and HgCl2 treatments of intact Chinese h...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90289-2
更新日期:1984-05-15 00:00:00
abstract::Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance. We therefore tested metformin alone and in combination with crizotinib in vivo, by...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114345
更新日期:2021-01-01 00:00:00
abstract::The binding of phenylbutazone (PB) to human serum albumin (HSA) at different pH and in the presence of different NaSCN and urea concentrations that alter the conformation of the protein was examined qualitatively on the basis of extrinsic elliptical strength at 288 nm by means of circular dichroism (CD). The values of...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90595-a
更新日期:1992-03-03 00:00:00
abstract::The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the admin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90475-6
更新日期:1983-05-01 00:00:00
abstract::Phenobarbital (PB) and certain structurally-related compounds induce a variety of hepatic drug-metabolizing enzymes in many strains of rats. Thus, following administration of PB (300, 500 ppm), barbital (BB, 1500 ppm) or 5-ethyl-5-phenylhydantoin (EPH, 500 ppm), CYP2B1-mediated benzyloxyresorufin O-dealkylase activity...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90615-p
更新日期:1992-03-03 00:00:00
abstract::Substituted fentanyls are abused and cause rapid fatal overdose. As their pharmacology is not well characterized, we examined in vitro pharmacology and structure-activity relationships of 22 substituted fentanyls with modifications of the fentanyl propyl group, and conducted in silico receptor/ligand modeling. Affinit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114293
更新日期:2020-12-01 00:00:00
abstract::We have reported that in renal epithelial A6 cells flavones stimulate the transepithelial Cl- secretion by activating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and/or the Na+/K+/2Cl- cotransporter. On the other hand, it has been established that cAMP activates the CFTR Cl- channel and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.10.026
更新日期:2004-02-15 00:00:00
abstract::The antithyroid drug propylthiouracil (PTU) has been shown previously to reduce hepatic oxygen utilization and to protect the liver from ethanol-induced injury. The present study examined the effect of PTU on hepatic microsomal oxygen consumption and on the activities of NADPH-cytochrome P450 reductase (CYP-reductase)...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00007-m
更新日期:1995-03-30 00:00:00
abstract::PepT1 (SLC15A1) is a high-capacity low-affinity transporter that is important in the absorption of digested di/tripeptides from dietary protein in the small intestine. PepT1 is also crucial for the intestinal uptake and absorption of therapeutic agents such as the β-lactam aminocephalosporins and antiviral prodrugs. S...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.03.008
更新日期:2016-05-01 00:00:00
abstract::Heat shock protein 90 (Hsp90) is a molecular chaperone engaging in multiple cellular signaling by stabilizing oncoproteins (e.g. Akt and c-Raf) in tumor cells. Whereas Hsp90 inhibitors such as 17-AAG exert promising antitumor effects in clinical trials, current efforts focus on developing agents targeting Hsp90 with i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.02.003
更新日期:2013-05-01 00:00:00
abstract::Treatment of rats with carbon tetrachloride (CCl4) resulted in early reproducible losses of either one or two specific polypeptides (depending on the inducing agent with which the animals had been treated) in the molecular weight range of the multiple forms of cytochrome P-450. The loss was correlated with a decrease ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90439-7
更新日期:1982-03-01 00:00:00
abstract::We tested the influence of IFNgamma on proteasome activity in parental Hep G2 cells that do not metabolize ethanol, as well as in recombinant Hep G2-derived cells that express either or both alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1). IFNgamma treatment increased proteasome activity in VL-17A (ADH(+),...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00252-1
更新日期:2003-09-01 00:00:00
abstract::The microbial alkaloid staurosporine is a member of a recently described family of protein kinase inhibitors. [N,N-dimethyl-3H]N-dimethylstaurosporine ([3H]DMS) was prepared from staurosporine by methylation with [3H]methyl iodide. Since staurosporine inhibits protein kinase C (PKC) most potently, the binding of [3H]D...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90697-j
更新日期:1990-07-15 00:00:00
abstract::Matrix metalloproteinases (MMPs), A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) are zinc-dependent endopeptidases that play a critical role in the destruction of extracellular matrix proteins and, the shedding of membrane-bound receptor molecules ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2019.02.033
更新日期:2019-07-01 00:00:00
abstract::Nucleoside diphosphokinase (NDK) of human platelets has been purified by chromatography on Blue Sepharose CL-6B gel (purification factor of 950) and shown to be free of adenylate kinase, ATPase and adenylate cyclase. The molecular weight was 70,000 with subunits of 17,000. The pH optimum was 8.0 Km values for ATP and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90762-8
更新日期:1986-12-15 00:00:00
abstract::The tissue distribution of captopril, an antihypertensive drug possessing a free sulfhydryl group, and its sulfur-conjugated metabolites was studied in rats by gas chromatography-mass spectrometry at 15, 30 and 60 min following a single 10 mg/kg oral dose of captopril. It was found that tissue accumulation of captopri...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90328-3
更新日期:1983-05-15 00:00:00
abstract::During attempts to isolate and identify an endogenous ligand for the glycoside binding sites on Na+,K+-ATPase, bovine adrenal glands were found to contain a potent inhibitor of isolated Na+,K+-ATPase. The inhibitory principle was extracted from adrenal cortex, following homogenization in NaHCO3 solution and separation...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90537-4
更新日期:1985-07-15 00:00:00
abstract::The effect of natural polyphenols on three isoforms of NO-synthase was investigated. Among the compounds tested, tannin was the most potent, inhibiting endothelial constitutive NO synthase (eNOS) with an IC50 of 2.2 microM. Other NOS isoforms (i.e. neuronal constitutive NOS and smooth muscle inducible NOS) were also i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00433-m
更新日期:1995-02-14 00:00:00
abstract::The aim of the present study was to investigate the effects of myricitrin, a flavonoid with anti-inflammatory and antinociceptive action, upon persistent neuropathic and inflammatory pain. The neuropathic pain was caused by a partial ligation (2/3) of the sciatic nerve and the inflammatory pain was induced by an intra...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.08.028
更新日期:2006-12-15 00:00:00
abstract::Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanate...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.03.044
更新日期:2004-09-15 00:00:00