Abstract:
:Inhibition of endosomal acidification disturbs insulin signaling in both liver and adipose cells. In this study we used MIN6 beta cells to determine whether bafilomycin, a potent inhibitor of the proton-translocating vacuolar ATPase, disrupts insulin signaling in islet beta cells. Pretreatment of MIN6 cells with varying concentrations of bafilomycin according to a time course revealed concentration and time-dependent changes in phosphorylation of insulin receptor signaling components. Increased phosphorylation of insulin receptor (IR), IRS2 and Akt was prolonged at low bafilomycin concentrations (10 and 50 nmol/L), whereas at high concentrations (100 and 200 nmol/L) phosphorylation rapidly returned to basal levels or below. Akt activation was demonstrated by transient increases in phosphorylation of BAD, cytoplasmic retention of FoxO1 and increased preproinsulin mRNA. Bcl2 expression was also transiently increased but reduced after 30 min exposure to bafilomycin, and this coincided with reduced cell viability. Thus, in beta cells inhibition of endosomal acidification by low concentrations of bafilomycin transiently increases insulin signaling, whereas high concentrations promote cell death. Bafilomycin and other agents that interfere with insulin signaling may contribute to diabetes development through disturbing homeostatic control of beta cell growth.
journal_name
Cell Biol Toxicoljournal_title
Cell biology and toxicologyauthors
Hettiarachchi KD,Zimmet PZ,Myers MAdoi
10.1007/s10565-006-0054-8subject
Has Abstractpub_date
2006-05-01 00:00:00pages
169-81issue
3eissn
0742-2091issn
1573-6822journal_volume
22pub_type
杂志文章abstract::Oxidative cell injury could be induced by different reactive oxygen species (ROS) operating in multiple pathways. The present work is focused on three different models of oxidative stress: the xanthine/xanthine oxidase system (XXO), an extracellular superoxide anion generator; tert-butylhydroperoxide (TBHP), an analog...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-009-9120-3
更新日期:2010-04-01 00:00:00
abstract::Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as a serious event has high mortality and medical costs. Systemic inflammation and immune response are the major factors influencing the outcome and quality of patient with AECOPD. On basis of identification and validation of AECOPD-specific inflamma...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-017-9405-x
更新日期:2018-04-01 00:00:00
abstract::The polyether toxin, okadaic acid, causes diarrhetic shellfish poisoning in humans. Despite extensive research into its cellular targets using rodent models, we know little about its putative effect(s) on innate immunity. We inoculated larvae of the greater wax moth, Galleria mellonella, with physiologically relevant ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-018-09448-2
更新日期:2019-06-01 00:00:00
abstract::To select an insert suitable for human umbilical vein endothelial cell (HUVEC) culture, we compared several available inserts of 0.2 to 0.45 micron porosity: Cellagen (ICN), Transwell-COL (Costar), Millicell-HA and CM (Millipore), Anopore (Nunc), Cyclopore (Falcon) in comparison with a control surface (Thermanox). The...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00438147
更新日期:1996-12-01 00:00:00
abstract::Folic acid (FA) is a vitamin essential for normal cellular functions, growth, and development. Because humans cannot synthesize this micronutrient, it must be obtained from dietary sources through intestinal absorption. The intestinal tract is a major target for oxidative stress. Our aim was to investigate the effect ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-012-9228-8
更新日期:2012-12-01 00:00:00
abstract::This study was implemented to test the Episkin model of reconstructed epidermis in the evaluation of the efficacy of cosmetic or dermopharmaceutical products on cutaneous energy metabolism. The energy metabolism is evaluated by measuring the concentration of intracellular ATP by a method using an ultrasensitive biolum...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00755786
更新日期:1994-12-01 00:00:00
abstract::Galectin 3 (Gal-3) is upregulated in gastric epithelial cells as a host response to Helicobacter pylori infection. However, the significance of Gal-3 expression in H. pylori-infected cells is not well established. We analyzed Gal-3 intracellular expression, localization, and its effects in H. pylori-infected gastric e...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-016-9315-3
更新日期:2016-02-01 00:00:00
abstract::Although the interactions of sulfur mustard (HD) with nucleic acids and proteins have been well studied, the toxic interactions with the membrane matrix and specially the phospholipid bilayer have so far been poorly investigated. We have used several NMR techniques to study these interactions: 1H NMR to observe the lo...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1020815723009
更新日期:2002-01-01 00:00:00
abstract::Human tumor cells have properties in vitro or in surrogate hosts that are distinct from those of normal cells, such as immortality, anchorage independence, and tumor formation in nude mice. However, different cells from individual tumors may exhibit some, but not all of these features. In previous years, human tumor c...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1007419810705
更新日期:1997-10-01 00:00:00
abstract::In order to clarify the protective mechanism of sodium molybdate against the acute toxicity of cadmium chloride in rat, the effect of in vivo sodium molybdate pretreatment on the cytotoxic action of cadmium in isolated hepatocytes was studied. The cytosolic pH of hepatocytes isolated from untreated rats immediately de...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00124071
更新日期:1991-10-01 00:00:00
abstract::The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated. Activation of nuclear factor kappaB (NF-kappaB) is initiated by the...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1023/a:1015384201785
更新日期:2002-01-01 00:00:00
abstract::The mutation rates of tumor suppressor protein p53 gene (TP53) are high in lung adenocarcinoma and promote the development of acquired drug resistance. The present study evaluated the p53-dependent role in lung cancer cell sensitivity to PI3K-specific inhibitors, PI3K-associated inhibitors, PI3K-non-related inhibitors...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-020-09523-7
更新日期:2020-10-01 00:00:00
abstract::The ubiquitin proteasome-proteolytic pathway has emerged as one of the most significant pathways in modulating protein homeostasis under both normal and disease states. The use of proteasome inhibitors (PI) has played a pivotal role in understanding protein turn over. The main objective of this work was to develop a c...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-010-9175-1
更新日期:2011-04-01 00:00:00
abstract::The article Is the clinical lipidomics a potential goldmine?, written by Linlin Zhang, Xianlin Han and Xiangdong Wang, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 21 July 2018 with open access. With the author(s)' decision to step. ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章,已发布勘误
doi:10.1007/s10565-019-09490-8
更新日期:2020-06-01 00:00:00
abstract::Recent findings suggest a functional interaction of the drug resistance enzyme glutathione S-transferase P (GSTP) with the transcription factor Nrf2, a master regulator of the adaptive stress response to cellular electrophiles. The effect of this interaction on the metabolism and redox of cellular thiols was investiga...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-020-09517-5
更新日期:2020-08-01 00:00:00
abstract::An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00757627
更新日期:1995-10-01 00:00:00
abstract:BACKGROUND:Heat shock proteins (HSP) are induced during cellular stress. Their role is to chaperone cellular proteins giving protection from denaturation and ultimately preventing cell death. Monocytes are key cells involved in atherosclerosis and are highly responsive to HSP induction. Therefore, we wished to examine ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-009-9134-x
更新日期:2010-06-01 00:00:00
abstract::The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial r...
journal_title:Cell biology and toxicology
pub_type: 杂志文章,评审
doi:10.1007/s10565-019-09461-z
更新日期:2019-10-01 00:00:00
abstract::The mesothelial cells (MCs) play an important role in the morpho-functional alterations of the peritoneal membrane (PM) undergoing peritoneal dialysis (PD). MCs, through the epithelial-mesenchymal transition process (EMT), progressively acquire a myofibroblast-like phenotype, promoting peritoneal fibrosis (PF) and fai...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-018-9438-9
更新日期:2019-04-01 00:00:00
abstract::The study investigates the effect of fenugreek seed polyphenol extract (FPEt) on ethanol-induced damage in rat liver. Chronic ethanol administration (6 g kg(-1) day(-1) x 60 days) caused liver damage that was manifested by excessive formation of thiobarbituric-acid-reactive substances, lipid hydroperoxides, and conjug...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-007-9050-x
更新日期:2008-10-01 00:00:00
abstract::We investigated mitogen-activated protein kinase (MAPK) pathways as well as reactive oxygen species (ROS) in olaquindox-induced apoptosis. Exposure of HepG2 cells to olaquindox resulted in the phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK). To confirm the role of p38 MAPK and JNK, HepG2 cells were pret...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-013-9249-y
更新日期:2013-08-01 00:00:00
abstract::Transforming growth factor-beta1 (TGF-beta1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The mechanism of this activation is not well elucidated. Here, we explore the role of TGF-beta/Smads signaling compounds in TGF-beta1-mediated activation of extracellular signal-regulated kinase ...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-006-0097-x
更新日期:2007-03-01 00:00:00
abstract::Sensitivity of baker's yeast to disulfiram (DSF) and hypersensitivity of a mutant devoid of Cu, Zn-superoxide dismutase to this compound is reported, demonstrating that yeast may be a simple convenient eukaryotic model to study the mechanism of DSF toxicity. DSF was found to induce oxidative stress in yeast cells demo...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-011-9200-z
更新日期:2012-02-01 00:00:00
abstract::The mouse skin cocarcinogens fluoranthene, pyrene, and undecane were used with the indirect-acting carcinogen, benzo(a)pyrene (BP), and the direct-acting alkylating carcinogen, beta-propiolactone (BPL), in an in vitro transformation assay. Dose response, cytotoxicity, and transformation studies with these compounds we...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/BF00118197
更新日期:1985-10-01 00:00:00
abstract::The heat-stable enterotoxin (Y-STa) produced by the pathogenic strains of Yersinia enterocolitica is a causative agent of secretory diarrhea. We have reported earlier that Y-STa-induced inositol trisphosphate-mediated cytosolic calcium rise occurs in rat intestinal epithelial cells. In the present communication, the i...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-008-9084-8
更新日期:2009-06-01 00:00:00
abstract::Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON pro...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-020-09525-5
更新日期:2021-02-01 00:00:00
abstract::Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation f...
journal_title:Cell biology and toxicology
pub_type: 杂志文章,评审
doi:10.1007/s10565-016-9377-2
更新日期:2017-06-01 00:00:00
abstract::We have previously synthesized various diazenecarboxamides (subsequently referred to as diazenes) that were cytotoxic to several tumor cell lines. To increase their biological activity, the structure has been modified appropriately. In the present study we examined the effects of N(1)-phenyl-N(2)-(2-pyridinylmethyl)di...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-006-0023-2
更新日期:2006-01-01 00:00:00
abstract::Sea urchin embryos and larvae represent suitable model systems on where to investigate the effects of heavy metals on development and cell viability. Here, we tested the toxic effects of low (10(-12 )M), medium (10(-9 )M), and high (10(-6 )M) cadmium chloride concentrations, mimicking unpolluted, moderately and highly...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-008-9066-x
更新日期:2008-12-01 00:00:00
abstract::Presently, a large effort is being made worldwide to increase the sustainability of industrial development, while preserving not only the quality of the environment but also that of animal and human life. In this work, sea urchin early developmental stages were used as a model to test the effects of the organophosphat...
journal_title:Cell biology and toxicology
pub_type: 杂志文章
doi:10.1007/s10565-008-9061-2
更新日期:2008-12-01 00:00:00