scholarly journals Effects of berberine on the pharmacokinetics of florfenicol and levels of cytochrome P450 3A37, multidrug resistance 1, and chicken xenobiotic‐sensing orphan nuclear receptor mRNA expression in broilers

2021 ◽  
Author(s):  
Sicong Li ◽  
Bin Wang ◽  
Min Zhang ◽  
Dingsheng Yuan ◽  
Jinliang Li ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Multidrug Resistance ◽  
Mrna Expression ◽  
Nuclear Receptor ◽  
Orphan Nuclear Receptor ◽  
Receptor Mrna

Nuclear receptor mRNA expression by HBV in human hepatoblastoma cell lines

2011 ◽  
Vol 312 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Shuang Wu ◽  
Tatsuo Kanda ◽  
Fumio Imazeki ◽  
Shingo Nakamoto ◽  
Hiroshi Shirasawa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Nuclear Receptor ◽  
Receptor Mrna

Differences in Cytochrome P450 and Nuclear Receptor mRNA Levels in Liver and Small Intestines between SD and DA Rats

2008 ◽  
Vol 23 (3) ◽  
pp. 196-206 ◽  
Author(s):  
Atsushi Kawase ◽  
Akiyuki Fujii ◽  
Makiko Negoro ◽  
Ryosuke Akai ◽  
Miki Ishikubo ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Nuclear Receptor ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Small Intestines

Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1

2001 ◽  
Vol 355 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Roongsiri MUANGMOONCHAI ◽  
Despina SMIRLIS ◽  
Siew-Cheng WONG ◽  
Mina EDWARDS ◽  
Ian R. PHILLIPS ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cytochrome P450 ◽  
Nuclear Receptor ◽  
Constitutive Androstane Receptor ◽  
Proximal Promoter ◽  
Orphan Nuclear Receptor ◽  
Primary Hepatocytes ◽  
Transcription Factor Sp1 ◽  
Transformed Cell Lines ◽  
Xenobiotic Induction

The constitutive androstane receptor (CAR) activates the expression of a reporter gene attached to the phenobarbital-response element (PBRE) of the cytochrome P450 2B1 (CYP2B1) gene in response to the barbiturate phenobarbital and the plant product picrotoxin. The xenobiotic-mediated increase in transactivation occurs in transfected primary hepatocytes and in liver transfected by biolistic-particle-mediated DNA transfer, but not in the transformed cell lines HepG2, CV-1 and HeLa, which support only constitutive activation of gene expression by CAR. Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes. The nuclear receptor 1 (NR1) site of the PBRE is sufficient for CAR-mediated transactivation, but additional sequences within the PBRE, and hence the proteins that bind to them, are required for the interaction of CAR with SRC-1. The NR2 site of the PBRE binds proteins other than CAR, including an unidentified nuclear receptor heterodimerized with retinoid X receptor α. By binding to the proximal promoter of CYP2B1, the transcription factor Sp1 increases both basal transcription and xenobiotic-induced expression via the PBRE. Thus induction of CYP2B1 expression by xenobiotics is mediated by the nuclear receptor CAR and, for optimal expression, requires SRC-1 and Sp1.

A Novel Histone Deacetylase Inhibitor MCT-3 Augments Inhibition of Leukemia Cell Growth and Suppresses Induction of MMP-9 Expression by Azacitidine in HL-60 Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4151-4151
Author(s):  
Hongbin Liu ◽  
Penelope A. Mayes ◽  
Patrick Perlmutter ◽  
Joseph J. Mckendrick ◽  
Anthony E. Dear
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Mrna Expression ◽  
Histone Deacetylase ◽  
Nuclear Receptor ◽  
Early Phase ◽  
Caspase 3 ◽  
Orphan Nuclear Receptor ◽  
Demethylating Agents

Abstract Azacitidine (AZA), a demethylating agent, has recently been demonstrated to have efficacy in the treatment of myelodysplasia and acute myeloid leukemia. A potential concern when considering the use of this agent is a recent report demonstrating AZA-mediated re-activation of matrix metalloproteinase-9 (MMP-9) expression facilitating the invasive metastatic phenotype (Sato NM et al J Natl Cancer Inst. 2003 Feb 19;95(4):327–30). Histone deacetylase inhibitors (HDACi) are a recently identified class of agents with considerable in vitro and in vivo activity and early phase clinical efficacy in the treatment of haematological malignancies (Bolden JE Nat Rev Drug Discov. 2006 Sep;5(9):769–84). Pre-clinical in vitro studies suggest that addition of HDACi to 5-aza-2′-deoxycytidine, a derivative of AZA, enhances the efficacy of this agent (Yang H et al Leuk Res. 2005 Jul; 29(7):739–48) whilst early phase clinical trials identify therapeutic activity using a combination of demethylating agents and HDACi (Garcia-Manero G, Blood. 2006 Nov 15;108(10):3271–9). Our current study aimed to determine the in vitro activity and molecular mechanisms of action of the novel HDACi MCT-3, a derivative of Oxamflatin, a hydroxamate analogue, (Dear AE, et al, Org Biomol Chem, 2006, 4, 3778–3784) in the HL-60 cell line alone and combination with AZA. AZA (1.0 microM) and MCT-3 (2.5 microM) alone inhibited HL-60 cell growth over 24hrs by 40%, 30% respectively. The combination of AZA with MCT-3 inhibited HL-60 cell growth up to 50%. Real-time PCR demonstrated that AZA and MCT-3 alone increased p15INK4b and Caspase 3 mRNA expression 2 fold. A Combination of AZA with MCT-3 increased p15INK4b and Caspase 3 mRNA expression up to 2.5 and increased p21WAF1/CIP1 and the orphan nuclear receptor Nur77 expression 2 fold. A combination of AZA and MCT-3 significantly attenuated AZA-induced MMP-9 mRNA expression and proteolytic activity. AZA and MCT-3 alone reduce HL-60 cell growth in vitro. Addition of MCT-3 to AZA increased inhibition of cell growth, suggesting that this HDACi may have the potential for additive activity with demethylating agents. AZA and MCT-3 have similar effects on expression of genes implicated in cell cycle arrest and apoptosis. Increased expression of p21WAF1/CIP1 and the orphan nuclear receptor Nur77 via inhibition of cell cycle progression and enhanced apoptosis may in part be responsible for the enhanced anti-leukaemia activity of the combination of AZA and MCT-3. Importantly MCT-3 is able to inhibit AZA-mediated induction of MMP-9 expression.

Effects of Radiation on Drug Metabolism: A Review

2019 ◽  
Vol 20 (5) ◽  
pp. 350-360 ◽  
Author(s):  
Xiangyang Li ◽  
Jianxin Yang ◽  
Yijie Qiao ◽  
Yabin Duan ◽  
Yuanyao Xin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Multidrug Resistance ◽  
Ionizing Radiation ◽  
Environmental Pollution ◽  
Mrna Expression ◽  
Drug Transporters ◽  
Area Under The Curve ◽  
Optimal Dose ◽  
Cancer Resistance ◽  
Resistance Protein

Background: Radiation is the fourth most prevalent type of pollution following the water, air and noise pollution. It can adversely affect normal bodily functions. Radiation alters the protein and mRNA expression of drugmetabolizing enzymes and drug transporters and the pharmacokinetic characteristics of drugs, thereby affecting drug absorption, distribution, metabolism, and excretion. Therefore, it is important to study the pharmacokinetic changes in drugs under radiation. Methods: To update data on the effects of ionizing radiation and non-ionizing radiation caused by environmental pollution or clinical treatments on the protein and mRNA expression of drug-metabolizing enzymes and drug transporters. Data and information on pharmacokinetic changes in drugs under radiation were analyzed and summarized. Results: The effect of radiation on cytochrome P450 is still a subject of debate. The widespread belief is that higherdose radiation increased the expression of CYP1A1 and CYP1B1 of rat, zebrafish or human, CYP1A2, CYP2B1, and CYP3A1 of rat, and CYP2E1 of mouse or rat, and decreased that of rat’s CYP2C11 and CYP2D1. Radiation increased the expression of multidrug resistance protein, multidrug resistance-associated protein, and breast cancer resistance protein. The metabolism of some drugs, as well as the clearance, increased during concurrent chemoradiation therapy, whereas the half-life, mean residence time, and area under the curve decreased. Changes in the expression of cytochrome P450 and drug transporters were consistent with the changes in the pharmacokinetics of some drugs under radiation. Conclusion: The findings of this review indicated that radiation caused by environmental pollution or clinical treatments can alter the pharmacokinetic characteristics of drugs. Thus, the pharmacokinetics of drugs should be rechecked and the optimal dose should be re-evaluated after radiation.

scholarly journals The Orphan Nuclear Receptor, NOR-1, Is a Target of β-Adrenergic Signaling in Skeletal Muscle

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5217-5227 ◽  
Author(s):  
Michael A. Pearen ◽  
James G. Ryall ◽  
Megan A. Maxwell ◽  
Naganari Ohkura ◽  
Gordon S. Lynch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Mass ◽  
Nuclear Receptor ◽  
Cold Exposure ◽  
Small Interfering Rna ◽  
Muscle Cells ◽  
Orphan Nuclear Receptor ◽  
Expression Of Genes ◽  
Interfering Rna

β-Adrenergic receptor (β-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy. We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene expression associated with the regulation of lipid homeostasis. Subsequently it was demonstrated by another group that β-AR agonists and cold exposure-induced Nur77 expression in brown adipocytes and brown adipose tissue, respectively. Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77−/− animal model. These studies underscored the importance of understanding the role of NOR-1 in skeletal muscle. In this context we observed 30–480 min of β-AR agonist treatment significantly and transiently increased expression of the orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris) and C2C12 skeletal muscle cells. Specific β2- and β3-AR agonists had similar effects as the pan-agonist and were blocked by the β-AR antagonist propranolol. Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter. Stable exogenous expression of a NOR-1 small interfering RNA (but not the negative control small interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR-1 mRNA expression and led to changes in the expression of genes involved in the control of lipid use and muscle mass underscored by a dramatic increase in myostatin mRNA expression. Concordantly the myostatin promoter was repressed by NOR-1 expression. In conclusion, NOR-1 is highly responsive to β-adrenergic signaling and regulates the expression of genes controlling fatty acid use and muscle mass.

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