Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway.


:Ghrelin is a 28-amino-acid peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR) and strongly stimulates the release of growth hormone from the hypothalamus-pituitary axis. Previous studies have identified the important physiological effects of ghrelin on bone metabolism, such as regulating proliferation and differentiation of osteoblasts, independent of GH/IGF-1 axis. However, research on effects and mechanisms of ghrelin on osteoblast apoptosis is still rare. In this study, we identified expression of GHSR in MC3T3-E1 cells and determined the effects of ghrelin on the apoptosis of osteoblastic MC3T3-E1 cells and the mechanism involved. Our data demonstrated that ghrelin inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as determined by terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate nick end-labeling (TUNEL) and ELISA assays. Moreover, ghrelin upregulated Bcl-2 expression and downregulated Bax expression in a dose-dependent manner. Our study also showed decreased activated caspase-3 activity under the treatment of ghrelin. Further study suggested that ghrelin stimulated the phosphorylation of ERK and AKT. Pretreatment of cells with the ERK inhibitor PD98059, PI3K inhibitor LY294002, and GHSR-siRNA blocked the ghrelin-induced activation of ERK and AKT, respectively; however, ghrelin did not stimulate the phosphorylation of p38 or JNK. PD90859, LY294002 and GHSR-siRNA attenuated the anti-apoptosis effect of ghrelin in MC3T3-E1 cells. In conclusion, ghrelin inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, which may be mediated by activating the GHSR/ERK and GHSR/PI3K/AKT signaling pathways.


Toxicol Appl Pharmacol


Liang QH,Liu Y,Wu SS,Cui RR,Yuan LQ,Liao EY




Has Abstract


2013-11-01 00:00:00














  • A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. I. Development and validation of the model using experimental data in rats.

    abstract::The objective of this study was to develop a biologically based dynamic model for predicting the distribution and elimination of methyl mercury and its metabolite, inorganic mercury, under a variety of exposure scenarios in rats. A model is proposed based on a multicompartment approach; each compartment represents an ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Carrier G,Brunet RC,Caza M,Bouchard M

    更新日期:2001-02-15 00:00:00

  • Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children.

    abstract::Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Phookphan P,Navasumrit P,Waraprasit S,Promvijit J,Chaisatra K,Ngaotepprutaram T,Ruchirawat M

    更新日期:2017-02-01 00:00:00

  • Induction of CYP1A1 gene expression in mouse hepatoma cells by benzo[e]pyrene, a ligand of the 4S polycyclic hydrocarbon-binding protein.

    abstract::Hepa 1c1c7 (WT), TAOc1BPrc1 (CI), and BPrc1 (CII) mouse hepatoma cells were exposed to benzo[e]pyrene (B[e]P) or benzo[a]pyrene (B[a]P). B[e]P induced activity of a rat CYP1A1 reporter gene construct (-3015 to +2545 bp) by 1.8- to 2-fold and 5-fold in WT and CI cells, respectively. B[e]P caused a 2-fold induction of a...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Sterling K,Raha A,Bresnick E

    更新日期:1994-09-01 00:00:00

  • Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes.

    abstract::Mono-(2-ethylhexyl) phthalate (MEHP) is a widely studied Sertoli cell toxicant. Here we describe alterations in Sertoli cell vimentin filament distribution and the incidence of testicular germ cell apoptosis in young (28-day-old) Fischer rats that were treated with MEHP (2 microgram/kg, po) and killed 0, 3, 6, or 12 h...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Richburg JH,Boekelheide K

    更新日期:1996-03-01 00:00:00

  • Toxicity and toxicokinetics of metformin in rats.

    abstract::Metformin is a first-line drug for the treatment of type 2 diabetes (T2D) and is often prescribed in combination with other drugs to control a patient's blood glucose level and achieve their HbA1c goal. New treatment options for T2D will likely include fixed dose combinations with metformin, which may require preclini...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Quaile MP,Melich DH,Jordan HL,Nold JB,Chism JP,Polli JW,Smith GA,Rhodes MC

    更新日期:2010-03-15 00:00:00

  • Application of hepatic cytochrome b5/P450 reductase null (HBRN) mice to study the role of cytochrome b5 in the cytochrome P450-mediated bioactivation of the anticancer drug ellipticine.

    abstract::The anticancer drug ellipticine exerts its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. The present study has examined the role of cytochrome P450 oxidoreductase (POR) and cytochrome b5 (Cyb5), electron donors to P450 enzymes, in the CYP-mediated metabolism and disposition of elliptic...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Reed L,Indra R,Mrizova I,Moserova M,Schmeiser HH,Wolf CR,Henderson CJ,Stiborova M,Phillips DH,Arlt VM

    更新日期:2019-03-01 00:00:00

  • Actions of juglone on energy metabolism in the rat liver.

    abstract::Juglone is a phenolic compound used in popular medicine as a phytotherapic to treat inflammatory and infectious diseases. However, it also acts as an uncoupler of oxidative phosphorylation in isolated liver mitochondria and, thus, may interfere with the hepatic energy metabolism. The purpose of this work was to evalua...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Saling SC,Comar JF,Mito MS,Peralta RM,Bracht A

    更新日期:2011-12-15 00:00:00

  • Deciding which chemical mixtures risk assessment methods work best for what mixtures.

    abstract::The most commonly used chemical mixtures risk assessment methods involve simple notions of additivity and toxicological similarity. Newer methods are emerging in response to the complexities of chemical mixture exposures and effects. Factors based on both science and policy drive decisions regarding whether to conduct...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审


    authors: Teuschler LK

    更新日期:2007-09-01 00:00:00

  • Inhibition of lymphocyte activation in splenic and gut-associated lymphoid tissues following oral exposure of mice to 7,12-dimethylbenz[a]anthracene.

    abstract::The hypothesis that 7,12-dimethyl-benz[a]anthracene (DMBA) suppresses immune function in mice via an inhibition of lymphocyte activation was examined in these studies. Daily exposure of B6C3F1 mice to DMBA (cumulative doses of 1.4 to 140 mg/kg) via the oral route for 14 days was found to inhibit phytohemagglutinin (PH...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Burchiel SW,Davis DA,Gomez MP,Montano RM,Barton SL,Seamer LC

    更新日期:1990-09-15 00:00:00

  • Inhibition of Na,K-ATPase by cadmium: different mechanisms in different species.

    abstract::The mechanism of action of Cd on Na,K-ATPase was investigated in two "classical" model systems, the shark rectal gland and rabbit kidney outer medulla. In lyophilized plasma membranes from dogfish rectal gland Cd inhibited Na,K-ATPase activity after 30 min of preincubation with an I50 of 1.3 x 10(-5) M. K-Dependent p-...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Kinne-Saffran E,Hülseweh M,Pfaff C,Kinne RK

    更新日期:1993-07-01 00:00:00

  • Tumor necrosis factor involvement in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated endotoxin hypersensitivity in C57BL/6J mice congenic at the Ah locus.

    abstract::An experimental model of endotoxin-induced release of tumor necrosis factor-alpha (TNF) into the serum of C57BL/6J mice congenic at the Ah locus was used to investigate the effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on TNF production. TCDD exposure of Ah-responsive mice (Ahbb) resulted in a dose-dependent i...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Clark GC,Taylor MJ,Tritscher AM,Lucier GW

    更新日期:1991-12-01 00:00:00

  • Functional deficiency of aryl hydrocarbon receptor augments oxygen toxicity-induced alveolar simplification in newborn mice.

    abstract::Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. New BPD is characterized as having alveolar simplification. We reported previously that aryl hydrocarbon receptor (AhR) deficiency increased susceptibility to hyperoxic lung injury in adult mice, and this was associated ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Shivanna B,Zhang W,Jiang W,Welty SE,Couroucli XI,Wang L,Moorthy B

    更新日期:2013-03-15 00:00:00

  • Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates.

    abstract::Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review disc...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审


    authors: Slotkin TA

    更新日期:2004-07-15 00:00:00

  • Combining an in silico proarrhythmic risk assay with a tPKPD model to predict QTc interval prolongation in the anesthetized guinea pig assay.

    abstract::Human-based in silico models are emerging as important tools to study the effects of integrating inward and outward ion channel currents to predict clinical proarrhythmic risk. The aims of this study were 2-fold: 1) Evaluate the capacity of an in silico model to predict QTc interval prolongation in the in vivo anesthe...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Morissette P,Polak S,Chain A,Zhai J,Imredy JP,Wildey MJ,Travis J,Fitzgerald K,Fanelli P,Passini E,Rodriguez B,Sannajust F,Regan C

    更新日期:2020-03-01 00:00:00

  • Metallothionein protection of cadmium toxicity.

    abstract::The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research on this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tis...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审


    authors: Klaassen CD,Liu J,Diwan BA

    更新日期:2009-08-01 00:00:00

  • Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol.

    abstract::Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Salazar KD,Brinkerhoff CJ,Lee JS,Chiu WA

    更新日期:2015-11-01 00:00:00

  • Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts--a comparative study.

    abstract::Interference of exogenous chemicals with the aromatase enzyme can be useful as a tool to identify chemicals that could act either chemopreventive for hormone-dependent cancer or adverse endocrine disruptive. Aromatase is the key enzyme in the biosynthesis of steroids, as it converts androgens to estrogens. Certain fla...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: van Meeuwen JA,Nijmeijer S,Mutarapat T,Ruchirawat S,de Jong PC,Piersma AH,van den Berg M

    更新日期:2008-05-01 00:00:00

  • Influence of GSTs, CYP2E1 and mEH polymorphisms on 1, 3-butadiene-induced micronucleus frequency in Chinese workers.

    abstract::1,3-butadiene (BD) has been classified as a human carcinogen, however, the relationship between chromosomal damage and its metabolic polymorphisms is not clear. The present study used the CBMN assay to detect chromosomal damage in the peripheral lymphocytes of 166 exposed workers and 41 non-exposed healthy individuals...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Tan H,Wang Q,Wang A,Ye Y,Feng N,Feng X,Lu L,Au W,Zheng Y,Xia Z

    更新日期:2010-09-15 00:00:00

  • Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells.

    abstract::Arsenic contamination of drinking water and food threatens the health of hundreds of millions of people worldwide by increasing the risk of numerous diseases. Arsenic exposure has been associated with infectious lung disease in epidemiological studies, but it is not yet understood how ingestion of low levels of arseni...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Goodale BC,Rayack EJ,Stanton BA

    更新日期:2017-09-15 00:00:00

  • Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis.

    abstract::Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Gundala SR,Yang C,Mukkavilli R,Paranjpe R,Brahmbhatt M,Pannu V,Cheng A,Reid MD,Aneja R

    更新日期:2014-10-01 00:00:00

  • Analysis of the interaction of phytoestrogens and synthetic chemicals: an in vitro/in vivo comparison.

    abstract::In the evaluation of chemical mixture toxicity, it is desirable to develop an evaluation paradigm which incorporates some critical attributes of real world exposures, particularly low dose levels, larger numbers of chemicals, and chemicals from synthetic and natural sources. This study evaluated the impact of low leve...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Charles GD,Gennings C,Tornesi B,Kan HL,Zacharewski TR,Bhaskar Gollapudi B,Carney EW

    更新日期:2007-02-01 00:00:00

  • Toxicological studies on a benzofurane derivative. I. A comparative study with phenobarbital on rat liver.

    abstract::The benzofurane derivative benzbromarone (BBR) previously has led to liver tumor formation after long-term treatment of rats, but no indications of genotoxicity were detected. The present studies were designed to elucidate the mechanism(s) possibly involved in liver tumor formation by BBR. Female Wistar rats were used...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Parzefall W,Schuppler J,Barthel G,Meyer-Rogge B,Schulte-Hermann R

    更新日期:1990-12-01 00:00:00

  • Predicting the oral uptake efficiency of chemicals in mammals: combining the hydrophilic and lipophilic range.

    abstract::Environmental risk assessment requires models for estimating the bioaccumulation of untested compounds. So far, bioaccumulation models have focused on lipophilic compounds, and only a few have included hydrophilic compounds. Our aim was to extend an existing bioaccumulation model to estimate the oral uptake efficiency...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: O'Connor IA,Huijbregts MA,Ragas AM,Hendriks AJ

    更新日期:2013-01-01 00:00:00

  • DNA-protein crosslinks induced by nickel compounds in isolated rat lymphocytes: role of reactive oxygen species and specific amino acids.

    abstract::Isolated rat lymphocytes in salts-glucose medium (pH 7.2) were incubated with nickel chloride, nickel acetate, nickel sulfate, and a soluble form of nickel subsulfide (0-2 mM) at 37 degrees C for 2 h. The soluble form of nickel subsulfide induced a significant increase in DNA-protein crosslinks (DPXLs) (111%) beginnin...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Chakrabarti SK,Bai C,Subramanian KS

    更新日期:2001-02-01 00:00:00

  • The impact of dose rate on the neurotoxicity of acrylamide: the interaction of administered dose, target tissue concentrations, tissue damage, and functional effects.

    abstract::Health agencies are often required to predict the effects of long term low level exposure in humans based on annual data involving short-term high-level exposures. Uncertainties in extrapolation can be, in part, based on potentially different mechanism associated with different exposure scenarios. This study evaluated...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Crofton KM,Padilla S,Tilson HA,Anthony DC,Raymer JH,MacPhail RC

    更新日期:1996-07-01 00:00:00

  • Hyperammonemia, increased brain neutral and aromatic amino acid levels, and encephalopathy induced by cyanide in mice.

    abstract::The correlation among hyperammonemia, brain neutral amino acid, and encephalopathy induced by cyanide was investigated in mice. Subcutaneous injection of 10 mg/kg of potassium cyanide increased the levels of blood ammonia by 2.5-fold as compared to those of the corresponding controls and caused loss of consciousness i...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Yamamoto H

    更新日期:1989-07-01 00:00:00

  • Induced hepatotoxicity in female rats by aflatoxin B1 and ethynylestradiol interaction.

    abstract::Female Sprague-Dawley rats were treated with a single ip dose of aflatoxin B1 (AFB1) (3 or 6 mg/kg). Twenty-four hours later and weekly until killed, some of the rats treated with AFB1 were given ethynylestradiol (EE) by gavage at the dose of 13 mg/kg. One, three, six, and nine months following the beginning of the ex...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Kamdem L,Magdalou J,Siest G,Ban M,Zissu D

    更新日期:1983-01-01 00:00:00

  • Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles.

    abstract::Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Tal TL,Simmons SO,Silbajoris R,Dailey L,Cho SH,Ramabhadran R,Linak W,Reed W,Bromberg PA,Samet JM

    更新日期:2010-02-15 00:00:00

  • The comparative biologic and toxic potencies of polychlorinated biphenyls and polybrominated biphenyls.

    abstract::Aroclor 1254 and fireMaster BP-6, two commercial polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) preparations, exhibit comparable biologic and toxic effects. In the present study the commercial PBB was more active than Aroclor 1254 in causing thymic atrophy in male Wistar rats. However, a direct compa...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Andres J,Lambert I,Robertson L,Bandiera S,Sawyer T,Lovering S,Safe S

    更新日期:1983-09-15 00:00:00

  • Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus.

    abstract::A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Yang CW,Chang HY,Hsu HY,Lee YZ,Chang HS,Chen IS,Lee SJ

    更新日期:2017-10-01 00:00:00