Abstract:
AIM:Osteopontin (OPN), a multifunctional protein, has been reported to be protoxicant in acetaminophen hepatotoxicity. In this study, the mechanisms underlying the detrimental role of OPN in acetaminophen toxicity were explored. METHODS:Male C57BL/6 (wild-type, WT) and OPN(-/-) mice were administered with acetaminophen (500 mg/kg, ip). After the treatment, serum transaminase (ALT), as well as OPN expression, histology changes, oxidative stress and inflammation response in liver tissue were studied. Freshly isolated hepatocytes of WT and OPN(-/-) mice were prepared. RESULTS:Acetaminophen administration significantly increased OPN protein level in livers of WT mice. OPN expression was mainly localized in hepatic macrophages 6 h after the administration. In OPN(-/-) mice, acetaminophen-induced serum ALT release was reduced, but the centrilobular hepatic necrosis was increased. In OPN(-/-) mice, the expression of CYP2E1 and CYP1A2 in livers was significantly increased; GSH depletion and lipid peroxidation in livers were enhanced. On the other hand, OPN(-/-) mice exhibited less macrophage and neutrophil infiltration and reduced expression of proinflammatory cytokines TNF-α and IL-1α in livers. An anti-OPN neutralizing antibody significantly reduced acetaminophen-induced serum ALT level and inflammatory infiltration in livers of WT mice. CONCLUSION:OPN plays a dual role in acetaminophen toxicity: OPN in hepatocytes inhibits acetaminophen metabolism, while OPN in macrophages enhances acetaminophen toxicity via recruitment of inflammatory cells and production of proinflammatory cytokines.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
He CY,Liang BB,Fan XY,Cao L,Chen R,Guo YJ,Zhao Jdoi
10.1038/aps.2012.47subject
Has Abstractpub_date
2012-08-01 00:00:00pages
1004-12issue
8eissn
1671-4083issn
1745-7254pii
aps201247journal_volume
33pub_type
杂志文章abstract:AIM:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC). METHODS:The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2008.18
更新日期:2009-02-01 00:00:00
abstract:AIM:To study the effect and mechanism of pyronaridine (PND) on the reversal of multidrug resistance (MDR) in K562/A02 and MCF7/ADR cell lines with mdr1+. METHODS:MTT assay was used to determine the cells growth inhibition after incubation for 72 h in the presence of doxorubicin (DOX) with or without PND. Intracellular...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract:AIM:To investigate the effects of angiotensin II (Ang II) on corticotropin-releasing hormone (CRH) and argipressin (AVP) release from median eminence (ME) of hypothalamus during acute hypoxia in rats. METHODS:Simulated hypoxia was performed in a hypobaric chamber. CRH and AVP were determined by radioimmunoassay (RIA)....
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract:AIM:Cathepsin L is a lysosomal cysteine protease that plays important roles in cancer tumorigenesis, proliferation and chemotherapy resistance. The aim of this study was to determine how cathepsin L regulated the radiosensitivity of human glioma cells in vitro. METHODS:Human glioma U251 cells (harboring the mutant typ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.36
更新日期:2015-09-01 00:00:00
abstract::AIDS is presently treatable, and patients can have a good prognosis due to the success of highly active antiretroviral therapy (HAART), but it is still not curable or preventable. High toxicity of HAART, and the emergence of drug resistance add to the imperative to continue research into new strategies and interventio...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2005.00193.x
更新日期:2005-10-01 00:00:00
abstract:AIM:To investigate the mechanism of brain interleukin-1 beta (IL-1 beta) in reserpine-induced behavioral depression in rats. METHODS:Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 beta. RESULTS:Intraperitoneal injection of reserpine (0, 4, 6, and 8...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract:AIM:To isolate the G4 and G1 molecular forms of acetylcholinesterase in rat cortex for interpreting the therapeutical effect of the AChE inhibitor drugs. METHODS:Size exclusion chromatography and ultracentrifugation were used to isolate and ascertain the G4 and G1 molecular forms of AChE. RESULTS:After size exclusion...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract:AIM:To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. METHODS:Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05-10 μmol/L) for various lengths of time. For pharmacological experiments,...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.59
更新日期:2012-07-01 00:00:00
abstract:AIM:Adenosine monophosphate-activated protein kinase (AMPK), a vital regulator of glucose metabolism, may affect insulin secretion in beta-cells. However, the role of AMPK in beta-cell lipotoxicity remains unclear. Fenofibrate has been reported to regulate lipid homeostasis and is involved in insulin secretion in pancr...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00717.x
更新日期:2008-04-01 00:00:00
abstract::In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of bindi...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.132
更新日期:2018-03-01 00:00:00
abstract::Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in thi...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2005.00058.x
更新日期:2005-03-01 00:00:00
abstract:AIM:Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, which has shown anti-oxidant, anti-cancer and anti-inflammatory activities. In this study, we investigated the effects of hyperoside on human rheumatoid fibroblast-like synoviocytes (FLSs) in vitro and on mouse collagen...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.7
更新日期:2016-05-01 00:00:00
abstract:AIM:Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS:Cell proliferation, DNA fragmentation, Ann...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.15
更新日期:2014-06-01 00:00:00
abstract::DJ-1 is a multifunctional protein associated with cancers and autosomal early-onset Parkinson disease. Besides the well-documented antioxidative stress activity, recent studies show that DJ-1 has deglycation enzymatic activity and anti-ferroptosis effect. It has been shown that DJ-1 forms the homodimerization, which d...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00531-1
更新日期:2020-10-06 00:00:00
abstract::The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have se...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2016.84
更新日期:2017-01-01 00:00:00
abstract::For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0479-2
更新日期:2020-07-31 00:00:00
abstract::As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capaci...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/s41401-020-0415-5
更新日期:2020-07-01 00:00:00
abstract:AIM:To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS:The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resve...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00343.x
更新日期:2006-11-01 00:00:00
abstract:AIM:Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dua...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.129
更新日期:2013-12-01 00:00:00
abstract:AIM:To explore correlation of T helper 1 (Th1) and Th2 cytokine between the cortical layer and pulmonary airway in ovalbumin-induced rat asthma model. METHODS:Aerosol antigen-induced changes of inflammation in bronchoalveolar lavage fluids (BALF) and pulmonary histologic section in sensitized rats were investigated. C...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract:AIM:To investigate the molecular mechanism and signaling pathway by which fenoterol, a beta(2)-adrenergic receptor (beta(2)-AR) agonist, produces anti-inflammatory effects. METHODS:THP-1, a monocytic cell line, was used to explore the mechanism of beta(2)-AR stimulation in LPS-induced secretion of inflammatory cytokin...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.153
更新日期:2009-11-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Acta pharmacologica Sinica
pub_type: 已发布勘误
doi:10.1038/s41401-020-0444-0
更新日期:2020-07-06 00:00:00
abstract:AIM:Based on the structural analysis to reveal the mechanism of ligand binding to beta-secretase and the specificity of each binding sub-site. METHODS:Molecular dynamics was used to simulate on the ligand free beta-secretase and ligand bound beta-secretase. The trajectories were analyzed using the essential dynamics, ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract::Brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. Yet, there are autoimmune diseases in both organs. This review discusses the nature of immune reacti...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2010.149
更新日期:2010-09-01 00:00:00
abstract:AIM:To study the antioxidant, activity of Qizhu Tang (QZT) both in vivo and in vitro. METHODS:QZT consists of 4 herbal constituents (Rhizoma Atractylodis Macrocephalae, Poria cocos, Kadix Notoginseng, and Radix Astragali), each of the components and their combinations were examined in vitro for 1, 1-diphenyl-2-picrylh...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract:AIM:To examine the effect of tachykinins on the ascending reflex pathway in rat small intestine, we used different selective neurokinin (NK) receptor antagonists (RA): a) NK1-RA: GR-82334 and CP-96.345, b) NK2-RA: MEN-10.376 and L-659.877. The aim was further to investigate the effect of substance P (SP) on the ascendi...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (PCa), which can often develop into androgen-ligand-independent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory PCa require ligand-independent AR signaling for survival. As curr...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2007.00683.x
更新日期:2007-09-01 00:00:00
abstract:AIM:The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings. METHODS:Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine (10(-5) mol/L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::In an effort to develop effective alternative strategies that increase the therapeutic efficacy and minimize the systemic toxicity of chemotherapeutic agents, more efforts are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2007.00691.x
更新日期:2007-09-01 00:00:00
abstract:AIM:To investigate the influence of picroside II on hepatocyte apoptosis and its mechanism. METHODS:Morphological changes and quantification of apoptotic cells were determined under transmission electron microscopy and flow cytometry respectively. DNA fragmentation was visualized by agarose gel electrophoresis. Semi-q...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00729.x
更新日期:2005-06-01 00:00:00