Activation of c-Jun and suppression of phospho-p44/42 were involved in diphenylhydantoin-induced apoptosis of cultured rat cerebellar granule neurons.

Abstract:

AIM:To investigate possible intracellular signal molecules involved in diphenylhydantoin (DPH)-mediated apoptosis of cerebellar granule neurons (CGN) and explore possible molecular mechanisms of neurotoxicity of DPH. METHODS:Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel electrophoresis were used to test morphological and biological characters of primary CGN and cortical neurons (CN) in the presence or absence of 100 micromol/L DPH; Western blot and RT-PCR were employed to further investigate apoptotic/survival signal moleculars involved in the neuronal apoptotic signal transdution. RESULTS:DPH 100 micromol/L induced a typical apoptosis of CGN but had no toxicity on CN. Cerebellar granule neural apoptosis induced by 100 micromol/L DPH was significantly inhibited by pre-treatment with SB203580 (10 micromol/L) or CEP-11004 (1 micromol/L) for 1 h. DPH markedly upregulated the levels of phospho-c-Jun (active c-Jun), total c-Jun protein and c-jun mRNA in CGN. The levels of phospho-c-Jun dramatically elevated by DPH at 8 h were significantly inhibited by SB203580 (10 micromol/L) or CEP-11004 (1 micromol/L). Moreover, the activities of p44/42 (ERK1/ERK2), other members of MAP kinases and generally believed to be important survival effetors in CGN, were markedly suppressed. However, the activities of both JNK and p38 were little affected in the process of apoptosis of CGN induced by 100 micromol/L DPH. CONCLUSION:The selective toxicity of DPH on CGN is likely due to its ability to induce apoptosis of CGN, it is a process involved activation of c-Jun and suppression of the activity of p44/42.

journal_name

Acta Pharmacol Sin

authors

Zhao LZ,Su XW,Huang YJ,Qiu PX,Yan GM

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

539-48

issue

6

eissn

1671-4083

issn

1745-7254

journal_volume

24

pub_type

杂志文章
  • Traditional Chinese medicine targeting apoptotic mechanisms for esophageal cancer therapy.

    abstract::Esophageal cancer is one of the most common types of cancer in the world, and it demonstrates a distinct geographical distribution pattern in China. In the last decade, inducing apoptosis with traditional Chinese medicine (TCM) has become an active area in both fundamental and clinical research on cancer therapy. In t...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1038/aps.2015.116

    authors: Zhang YS,Shen Q,Li J

    更新日期:2016-03-01 00:00:00

  • Autophagy in ageing and ageing-associated diseases.

    abstract::Autophagy is a cell self-digestion process via lysosomes that clears "cellular waste", including aberrantly modified proteins or protein aggregates and damaged organelles. Therefore, autophagy is considered a protein and organelle quality control mechanism that maintains normal cellular homeostasis. Dysfunctional auto...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1038/aps.2012.188

    authors: He LQ,Lu JH,Yue ZY

    更新日期:2013-05-01 00:00:00

  • Thrombin induced connective tissue growth factor expression in rat vascular smooth muscle cells via the PAR-1/JNK/AP-1 pathway.

    abstract:AIM:To investigate the signaling pathways involved in thrombin-induced connective tissue growth factor (CTGF) expression in rat vascular smooth muscle cells (VSMCs). METHODS:Experiments were preformed on primary rat aortic smooth muscle cells (RASMCs) and a rat VSMC line (A10). CTGF protein levels were measured using ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2011.178

    authors: Ko WC,Chen BC,Hsu MJ,Tsai CT,Hong CY,Lin CH

    更新日期:2012-01-01 00:00:00

  • Effects of chiral 3-n-butylphthalide on apoptosis induced by transient focal cerebral ischemia in rats.

    abstract:AIM:To investigate the effects of 3-n-butylphthalide (NBP) on apoptosis induced by transient focal cerebral ischemia in rats, compare the action potency of s-(-)-, r-(+)- and (+/-)-NBP, and clarify the enantiomer that played a main role. METHODS:DNA fragmentation was detected by the terminal deoxynucleotidyl transfera...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Chang Q,Wang XL

    更新日期:2003-08-01 00:00:00

  • Viral and immunologic follow up of 4 to 9 years of AIDS treatments by quadruple combinations of virostatics including integrase inhibitors applied in short sequences differing by drug rotation.

    abstract:AIM:To present the 4 to 9 years (median: 6 years) treatment follow up of 10 HIV1-AIDS patients, 9 at AIDS and 1 at A3 stages. METHODS:We have applied from 1992 to 1994, AZT combined with 2 integrase inhibitors, acriflavine and hydroxy-methyl-ellipticine. We could shift, in 1994, to combinations of 3 drugs including tw...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Mathe G,Morette C,Hallard M,Pontiggia P,Blanquet D,Hage F

    更新日期:2002-01-01 00:00:00

  • Telomere shortening activates TGF-β/Smads signaling in lungs and enhances both lipopolysaccharide and bleomycin-induced pulmonary fibrosis.

    abstract::Telomere shortening is associated with idiopathic pulmonary fibrosis (IPF), a high-morbidity and high-mortality lung disease of unknown etiology. However, the underlying mechanisms remain largely unclear. In this study, wild-type (WT) mice with normal telomeres and generation 3 (G3) or G2 telomerase RNA component (TER...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/s41401-018-0007-9

    authors: Liu YY,Shi Y,Liu Y,Pan XH,Zhang KX

    更新日期:2018-11-01 00:00:00

  • Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line.

    abstract:AIM:To investigate the ability of an antisense RNA eukaryotic expression plasmid pcDNA3.1/survivin in down-regulating the expression level of survivin mRNA and survivin protein and reversed multidrug resistance (MDR) in adriamycin-resistant HL-60/ADR cell line. METHODS:The expression of survivin mRNA was measured by R...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Wang L,Zhang GM,Feng ZH

    更新日期:2003-12-01 00:00:00

  • Pharmacological and immunochemical characterization of alpha2* nicotinic acetylcholine receptors (nAChRs) in mouse brain.

    abstract:AIM:alpha2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of alpha2* nAChRs in these mouse brain regions. METHODS:alpha2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2009.68

    authors: Whiteaker P,Wilking JA,Brown RW,Brennan RJ,Collins AC,Lindstrom JM,Boulter J

    更新日期:2009-06-01 00:00:00

  • Effect of unsaturated fatty acid on muscarinic current in guinea pig gastric antral circular myocytes.

    abstract:AIM:To investigate the effect of ectogenesis unsaturated fatty acid on carbachol-induced muscarinic current (ICCh) and its mechanism. METHODS:Using the whole-cell patch-clamp technique, ICCh was recorded in single smooth muscle cell isolated from the antral circular smooth muscles of guinea-pig stomach. RESULTS:Arach...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Cui YF,Jin H,Guo HS,Li L,Yu YC,Xu WX

    更新日期:2003-03-01 00:00:00

  • Effect of valsartan and fosinopril on catecholamine-induced cardiac hypertrophy.

    abstract:AIM:To study the influence of angiotensin (Ang) II receptor antagonist (AT1) valsartan and angiotensin-converting enzyme (ACE) inhibitor fosinopril on the cardiac hypertrophy induced by catecholamine. METHODS:A cardiac hypertrophy model was produced by i.p. norepinephrine (NE) 1.5 mg.kg-1.d-1 x 15 d. The animals were ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Xiang Y,Huang J

    更新日期:2000-09-01 00:00:00

  • In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L.

    abstract:AIM:To examine the anti-cancer effects of chamaejasmenin B and neochamaejasmin C, two biflavonones isolated from the root of Stellera chamaejasme L (known as the traditional Chinese herb Rui Xiang Lang Du) in vitro. METHODS:Human liver carcinoma cell lines (HepG2 and SMMC-7721), a human non-small cell lung cancer cell...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2012.158

    authors: Zhang C,Zhou SS,Feng LY,Zhang DY,Lin NM,Zhang LH,Pan JP,Wang JB,Li J

    更新日期:2013-02-01 00:00:00

  • C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis.

    abstract::The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/s41401-018-0191-7

    authors: Chen Z,Tong LJ,Tang BY,Liu HY,Wang X,Zhang T,Cao XW,Chen Y,Li HL,Qian XH,Xu YF,Xie H,Ding J

    更新日期:2019-06-01 00:00:00

  • Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism.

    abstract::Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study,...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/s41401-018-0066-y

    authors: Qiao SG,Sun Y,Sun B,Wang A,Qiu J,Hong L,An JZ,Wang C,Zhang HL

    更新日期:2019-01-01 00:00:00

  • Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes.

    abstract::KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gli...

    journal_title:Acta pharmacologica Sinica

    pub_type: 临床试验,杂志文章

    doi:10.1038/aps.2016.103

    authors: Li Q,Tang TT,Jiang F,Zhang R,Chen M,Yin J,Bao YQ,Cheng X,Hu C,Jia WP

    更新日期:2017-01-01 00:00:00

  • Raisanberine protected pulmonary arterial rings and cardiac myocytes of rats against hypoxia injury by suppressing NADPH oxidase and calcium influx.

    abstract:AIM:To investigate the protection of pulmonary arterial rings and cardiac myocytes of rats by raisanberine (RS), a derivative of berberine, against hypoxia injury and to elucidate the action mechanisms. METHODS:Adult SD rats were exposed to intermittent hypoxia for 17 d or 28 d. The pulmonary arterial rings were isola...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2012.7

    authors: Gao J,Tang YQ,Dai DZ,Cheng YS,Zhang GL,Zhang C,Dai Y

    更新日期:2012-05-01 00:00:00

  • Distribution of angiotensin converting enzyme gene polymorphism among Northern Hans, Dahurs, and Ewenks.

    abstract:AIM:To observe the polymorphism of angiotensin-converting enzyme (ACE) gene in Northern Hans, Dahurs, and Ewenkis of China. METHODS:The polymerase chain reaction was used to type the insertion/deletion polymorphism at intron 16 of ACE gene among 90 Northern Hans, 84 Dahurs, and 64 Ewenkis individuals. The experiment d...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Zhang YM,Zhang LY,Wang KQ,Ge JB

    更新日期:2001-08-01 00:00:00

  • Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C.

    abstract:AIM:To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I(Ca,L)) in rat ventricular myocytes. METHODS:The whole-cell patch-clamp techniques were used to record I(Ca,L) in rat ventricular myocytes. RESULTS:Hyposmotic challenge(∼220 mosmol/L) induced biphasic c...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2010.112

    authors: Luo AT,Luo HY,Hu XW,Gao LL,Liang HM,Tang M,Hescheler J

    更新日期:2010-11-01 00:00:00

  • Hydrogen sulfide: third gaseous transmitter, but with great pharmacological potential.

    abstract::Hydrogen sulfide (H2S), which is well known traditionally as a toxic gas, has been proven to be produced endogenously by 3 enzymes in mammalian tissues and plays important roles in physiological and pathophysiological conditions. In the central nervous system, H2S functions as not only a neuromodulator, but also a neu...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1111/j.1745-7254.2007.00629.x

    authors: Chen CQ,Xin H,Zhu YZ

    更新日期:2007-11-01 00:00:00

  • Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery.

    abstract:AIM:To determine the release characteristics of a 5-fluorouracil-loaded poly (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the success of glaucoma filtration surgery in rabbit eyes. METHODS:A method of microspheres accumulated by excessive carriers was used in the preparation of the 5-F...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2008.00833.x

    authors: Cui LJ,Sun NX,Li XH,Huang J,Yang JG

    更新日期:2008-09-01 00:00:00

  • Expression of pro-inflammatory and anti-inflammatory cytokines in brain of atherosclerotic rats and effects of Ginkgo biloba extract.

    abstract:AIM:To study the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS:The experimental model of AS in rats were established by intraperitioneal injection of vit...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2005.00106.x

    authors: Jiao YB,Rui YC,Li TJ,Yang PY,Qiu Y

    更新日期:2005-07-01 00:00:00

  • Seipin mutation at glycosylation sites activates autophagy in transfected cells via abnormal large lipid droplets generation.

    abstract:AIM:Seipin is a protein that resides in endoplasmic reticulum, and involved in both lipid metabolic disorders and motor neuropathy. The aim of this study was to investigate the effects of mutant seipin on autophagy system and the morphology of lipid droplets in vitro. METHODS:HEK-293, H1299 and MES23.5 cells were tran...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2014.164

    authors: Fan HD,Chen SP,Sun YX,Xu SH,Wu LJ

    更新日期:2015-04-01 00:00:00

  • ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system.

    abstract::JFCR39 is an informatic anticancer drug discovery system that utilizes a panel of 39 human cancer cells coupled with a drug-activity database. This system not only provides disease-oriented information but can also predict the mechanism of action of a given antitumor agent. Development of a phosphatidylinositol 3-kina...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1038/aps.2010.150

    authors: Kong DX,Yamori T

    更新日期:2010-09-01 00:00:00

  • Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest.

    abstract:AIM:Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP w...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2012.20

    authors: Zheng SE,Xiong S,Lin F,Qiao GL,Feng T,Shen Z,Min DL,Zhang CL,Yao Y

    更新日期:2012-06-01 00:00:00

  • CJZ3, a lomerizine derivative, modulates P-glycoprotein function in rat brain microvessel endothelial cells.

    abstract:AIM:To investigate the modulatory effect of CJZ3, a lomerizine derivative, on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC). METHODS:RBMEC were isolated and cultured in Dulbecco modified Eagle medium/F12 (1:1) medium, and the amount of intracellular rhodamine 123 (Rh123) was determi...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2006.00294.x

    authors: Ji BS,He L,Li XQ,Liu GQ

    更新日期:2006-04-01 00:00:00

  • Antcin A, a steroid-like compound from Antrodia camphorata, exerts anti-inflammatory effect via mimicking glucocorticoids.

    abstract:AIM:To determine the active ingredient of Niuchangchih (Antrodia camphorata) responsible for its anti-inflammatory effects and the relevant molecular mechanisms. METHODS:Five major antcins (A, B, C, H, and K) were isolated from fruiting bodies of Niuchangchih. Structural similarity between the antcins and 2 glucocorti...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2011.36

    authors: Chen YC,Liu YL,Li FY,Chang CI,Wang SY,Lee KY,Li SL,Chen YP,Jinn TR,Tzen JT

    更新日期:2011-07-01 00:00:00

  • Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity.

    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

    authors: Sun CY,Hu Y,Guo T,Wang HF,Zhang XP,He WJ,Tan H

    更新日期:2006-11-01 00:00:00

  • Composite glycidyl methacrylated dextran (Dex-GMA)/gelatin nanoparticles for localized protein delivery.

    abstract:AIM:Localized delivery of growth factors has significant potential as a future therapeutic strategy in tissue engineering and regenerative medicine. A nanoparticle vehicle was created and evaluated in this study with the intent to deliver growth factors for periodontal regeneration. METHODS:Novel composite nanoparticl...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2009.15

    authors: Chen FM,Ma ZW,Dong GY,Wu ZF

    更新日期:2009-04-01 00:00:00

  • Rifampicin induces clathrin-dependent endocytosis and ubiquitin-proteasome degradation of MRP2 via oxidative stress-activated PKC-ERK/JNK/p38 and PI3K signaling pathways in HepG2 cells.

    abstract::It was reported that antituberculosis medicines could induce liver damage via oxidative stress. In this study, we investigated the effects of rifampicin (RFP) on the membrane expression of multidrug resistance-associated protein 2 (MRP2) and the relationship between oxidative stress and RFP-induced endocytosis of MRP2...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/s41401-019-0266-0

    authors: Xu BY,Tang XD,Chen J,Wu HB,Chen WS,Chen L

    更新日期:2020-01-01 00:00:00

  • Leukamenin F suppresses liver fibrogenesis by inhibiting both hepatic stellate cell proliferation and extracellular matrix production.

    abstract:AIM:To investigate the inhibitory effect of the natural product Leukamenin F on liver fibrosis and explore its potential underlying mechanisms. METHODS:Carbon tetrachloride (CCl(4))-treated mouse model in vivo and in hepatic stellate cells (HSC) in vitro were used. The effect on CCl(4)-induced liver fibrosis was studi...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2010.64

    authors: Liu Q,Wang X,Zhang Y,Li CJ,Hu LH,Shen X

    更新日期:2010-07-01 00:00:00

  • Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects.

    abstract:AIM:To study the stereoselectivity in pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1) in human subjects. METHODS:Trans-T hydrochloride sustained-release tablets were taken orally by 12 healthy male volunteers. After a multiple dosage schedule, th...

    journal_title:Acta pharmacologica Sinica

    pub_type: 临床试验,杂志文章

    doi:

    authors: Liu HC,Liu TJ,Yang YY,Hou YN

    更新日期:2001-01-01 00:00:00