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, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Digital images of neurons were analyzed for total neurite branch length (TNBL), neurite number, terminal branch number, and soma area by SPOT Advanced Imaging software. After incubation with atorvastatin for 48 h, the levels of phosphorylated 3-phosphoinoside-dependent protein kinase-1 (PDK1), phospho-Akt, phosphorylated mammalian target of rapamycin (mTOR), phosphorylated 4E-binding protein 1 (4E-BP1), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in the cortical neurons were evaluated using Western blotting analyses. RESULTS:Atorvastatin (0.05-10 μmol/L) resulted in dose-dependent increase in neurite number and length in these neurons. Pretreatment of the cortical neurons with phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 (30 μmol/L) and wortmannin (5 μmol/L), Akt inhibitor tricribine (1 μmol/L) or mTOR inhibitor rapamycin (100 nmol/L) blocked the atorvastatin-induced increase in neurite outgrowth, suggesting that atorvastatin promoted neurite outgrowth via activating the PI3K/Akt/mTOR signaling pathway. Atorvastatin (10 μmol/L) significantly increased the levels of phosphorylated PDK1, Akt and mTOR in the cortical neurons, which were prevented by LY294002 (30 μmol/L). Moreover, atorvastatin (10 μmol/L) stimulated the phosphorylation of 4E-BP1 and p70S6K, the substrates of mTOR, in the cortical neurons. In addition, atorvastatin (10 μmol/L) significantly increased the phosphorylated GSK-3β level in the cortical neurons, which was prevented by both LY294002 and tricribine. CONCLUSION:These results suggest that activation of both the PI3K/Akt/mTOR and Akt/GSK-3β signaling pathways is responsible for the atorvastatin-induced neurite outgrowth in cultured cortical neurons.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Jin Y,Sui HJ,Dong Y,Ding Q,Qu WH,Yu SX,Jin YXdoi
10.1038/aps.2012.59subject
Has Abstractpub_date
2012-07-01 00:00:00pages
861-72issue
7eissn
1671-4083issn
1745-7254pii
aps201259journal_volume
33pub_type
杂志文章abstract:AIM:To explore the effects of glutamine on growth and apoptosis of hepatoma cells. METHODS:Mice inoculated with hepatoma cell (H22) suspension subcutaneously at right axilla were orally administered with glutamine (GLN) solution. Human hepatoma cell culture (SMMC-7721) was treated with different concentrations of GLN ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:AIM:The interaction of anthracycline anticancer drugs with chromatin, nucleosomes and histone H1 has been extensively studied. In the present study, for the first time, we have investigated the binding of anthracycline antibiotic, daunomycin, to free and cross-linked thymus core histones (CL-core) in solution and in th...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00542.x
更新日期:2007-05-01 00:00:00
abstract:AIM:To investigate the effect of epigallocatechin gallate (EGCG) on angiotensin II (Ang II)-induced stress fiber formation and hyperpermeability in endothelial cells. METHODS:Human umbilical vein endothelial cells (HUVECs) were treated with Ang II in the absence or presence of EGCG or mitogen-activated protein kinases...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.75
更新日期:2010-10-01 00:00:00
abstract:AIM:To evaluate single-dose and multiple-dose pharmacokinetics of cytotoxic T-lymphocyte-associated antigen 4 fusion protein (CTLA4Ig) in healthy volunteers and patients with rheumatoid arthritis (RA). METHODS:The clinical trials included two phase I open studies: study 1 was an open-label dose-escalation study in 27 ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.13
更新日期:2009-03-01 00:00:00
abstract::miRNAs have shown promise as potential biomarkers for acute myocardial infarction (AMI). However, the current used quantitative real-time PCR (qRT-PCR) allows solely for relative expression of nucleic acids and it is susceptible to day-to-day variability, which has limited the validity of using the miRNAs as biomarker...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.136
更新日期:2018-07-01 00:00:00
abstract:AIM:Our previous study demonstrated an siRNA-mediated, allele-specific silencing of mutant genes that cause amyotrophic lateral sclerosis. To improve siRNA design for better therapeutic use of RNA interference, we systematically tested the base-pairing mismatch strategy in the design of asymmetric siRNA. METHODS:A nat...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00740.x
更新日期:2008-02-01 00:00:00
abstract:AIM:The purpose of this study was to reveal the effects of hepatocyte growth factor (HGF) variants on human breast cancer cells and the differential signaling pathways of the variants in controlling cell proliferation and invasion. METHODS:Four HGF variants (NK1, NK2, NK3, and NK4) were created by gene engineering, an...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00799.x
更新日期:2008-06-01 00:00:00
abstract:AIM:To examine whether selective serotonin reuptake inhibitor citalopram interacts with Kv1.5, one of the cardiovascular-specific Kv channel isoforms. METHODS:The interaction between citalopram and Kv1.5 expressed in Chinese hamster ovary cells was studied using the whole-cell patch-clamp technique. RESULTS:Citalopra...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.14
更新日期:2010-04-01 00:00:00
abstract:AIM:To examine the effects of β3-adrenoceptor (β3-AR) activation on atherosclerotic plaque development in ApoE(-/-) mice. METHODS:Thirty six week-old male ApoE(-/-) mice on a high-fat diet were treated with atorvastatin (10 mg·kg(-1)·d(-1), po), BRL37344 (β3-AR agonist, 1.65 or 3.30 μg/kg, ip, twice a week) or SR52390...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.70
更新日期:2013-09-01 00:00:00
abstract::The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency virus) drug target owning to its pivotal role in HIV-1 viral entry as a co-receptor. Here, we present a 2.9 Å resolution crystal structure of CCR5 bound to PF-232798, a second-generation oral CCR5 antagonist currently in phase II clinical tri...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-018-0054-2
更新日期:2019-04-01 00:00:00
abstract::Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood-brain barrier. Our previous works show that bile duct ligation (BDL) impair...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0242-8
更新日期:2020-02-01 00:00:00
abstract:AIM:To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms. METHODS:Male mice received nimesulide 10 mg/kg, 20 mg/kg, and 40 mg/kg ig daily for 21 d. Electron microscopy (EM), flow cytometry (FCM), DNA ladder, radioimmunoass...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract:AIM:Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS:In ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.117
更新日期:2016-03-01 00:00:00
abstract::Diabetic nephropathy (DN) is characterized by sterile inflammation with continuous injury and loss of renal inherent parenchyma cells. Podocyte is an essential early injury target in DN. The injury and loss of podocytes are closely associated with proteinuria, the early symptom of renal injury in DN. However, the exac...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00525-z
更新日期:2020-09-23 00:00:00
abstract::The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-018-0087-6
更新日期:2018-12-01 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:Toxicity of retinol (vitamin A) has been previously associated with apoptosis and/or cell malignant transformation. Thus, we investigated the pathways involved in the induction of proliferation, deformation and proliferative focus formation by retinol in cultured Sertoli cells of rats. METHODS:Sertoli cells were i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.202
更新日期:2012-04-01 00:00:00
abstract:AIM:To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro. METHODS:The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.46
更新日期:2012-07-01 00:00:00
abstract::A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin (100 mg·kg-1·d-1...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.18
更新日期:2017-10-01 00:00:00
abstract:AIM:To examine whether (-)-stepholidine (SPD) has a direct effect on the N-methyl- D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz). METHODS:NMDAR was transiently expressed in human embryonic kidney 293 (...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00581.x
更新日期:2007-07-01 00:00:00
abstract::Etimicin (ETM), a fourth-generation aminoglycosides (AGs), is now widely clinically used in China due to its high efficacy and low toxicity. However, the mechanisms underlying its low nephrotoxicity and ototoxicity remain unclear. In the present study we compared the antibacterial and toxicity profiles of etimicin, ge...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0342-5
更新日期:2020-06-01 00:00:00
abstract:AIM:To investigate the mechanisms underlying the isomer-selective distribution of 3-n-butylphthalide (NBP) hydroxylated metabolites, 3-hydroxy-NBP (3-OH-NBP) and 10-hydroxy-NBP (10-OH-NBP), across the blood brain barrier (BBB). METHODS:After oral administration of NBP (20 mg/kg) to rats, the pharmacokinetics of two ma...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.64
更新日期:2015-12-01 00:00:00
abstract:AIM:To evaluate the pharmacokinetic characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C. METHODS:After the synthesis of L-valyl-ara-C, the in vitro stability of L-valyl-ara-C was examined in various biological media. Plasma pharmacokinetic profiles of ara-C and L-valyl-ara-C were also evaluated in rats...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00474.x
更新日期:2007-02-01 00:00:00
abstract:AIM:To evaluate the nasal absorption enhancement of insulin by sodium deoxycholate (SDC) in combination with cyclodextrins (CD). METHODS:The concentration of glucose in blood was measured. Scanning electron microscopy technique was used to investigate the effect of enhancers on the nasal mucocilia. The effect of SDC i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract:AIM:To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS:Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were tre...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.133
更新日期:2014-01-01 00:00:00
abstract:AIM:To study the effects of MN-9202, a new effective Ca2+ channel blocker, on platelet aggregation, 5-HT and TXB2 release, and calcium transport induced by platelet activators. METHODS:The mobilization of cytosolic-free calcium induced by thrombin in washed platelets was observed by Ca(2+)-sensitive fluorescent indica...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:AIM:To investigate whether IL-12p40 plays a crucial role in regulating islet allograft rejection in a streptozotocin (STZ)-induced diabetes mouse model. METHODS:C57BL/6 and IL-12p40 gene knockout mice were selected as recipient mice, to which the diabetes was induced with a treatment of STZ (150-200 mg/kg) by a single...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00341.x
更新日期:2006-08-01 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:AIM:KCNQ1 and KCNE1 form a complex in human ventricular cardiomyocytes, which are important in maintaining a normal heart rhythm. In the present study we investigated the effects of a homologous series of 1-alkanols on KCNQ1/KCNE1 channels expressed in Xenopus oocytes. METHODS:ECG recording was made in rats injected w...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.133
更新日期:2016-01-01 00:00:00
abstract::Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2015.73
更新日期:2015-10-01 00:00:00