Tetracyclines cause cell stress-dependent ATF4 activation and mTOR inhibition.

Abstract:

:Tetracyclines have long been used as valuable broad-spectrum antibiotics. The high antibacterial activity of tetracyclines, combined with their good tolerability, has led to their widespread use in treating various infectious diseases. However, similar to other antibiotics, tetracyclines are also known for their adverse effects on different human tissues, including hepatic steatosis. We observed that tetracyclines, including doxycycline and minocycline, caused enhanced expression of the liver chalone inhibin βE in HepG2 cells, mediated by the cell stress-regulated transcription factor ATF4. ATF4 and its target genes ATF3, CHOP, and inhibin βE are involved in cell cycle control, cell survival, cell metabolism, and modulation of cytokine expression. Furthermore, we observed that long term tetracycline incubation also caused inhibition of the mTOR complex, a central regulator of cell metabolism, further contributing to the observed cell-cycle arrest and autophagy in doxycycline- and minocycline-treated cell lines. ATF4 activation and mTOR inhibition link two crucial regulators of the cellular stress response and cell metabolism to the effects of tetracyclines on eukaryotic cell metabolism, and may help to understand the antibiotic-independent influence of these drugs on human tissues. Since the observed effects of tetracyclines on human cells were also found to be dependent on the magnesium ion concentrations supplied, the data further indicate the importance of magnesium supplementation to reduce or prevent side effects of long term treatment with tetracyclines.

journal_name

Exp Cell Res

authors

Brüning A,Brem GJ,Vogel M,Mylonas I

doi

10.1016/j.yexcr.2013.11.012

subject

Has Abstract

pub_date

2014-01-15 00:00:00

pages

281-9

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(13)00500-4

journal_volume

320

pub_type

杂志文章
  • Functional characterization of the spontaneously transformed human umbilical vein endothelial cell line ECV304: use in an in vitro model of angiogenesis.

    abstract::To gain insight into the role of the endothelial cell during the pathophysiology of the angiogenic response, investigators have isolated micro- and macrovascular endothelial cells from a wide range of both animal and human vessels, including the umbilical vein. Human umbilical vein endothelial cells (HUVECs) isolated ...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1996.0168

    authors: Hughes SE

    更新日期:1996-05-25 00:00:00

  • The N-terminal domain of the mammalian nucleoporin p62 interacts with other nucleoporins of the FXFG family during interphase.

    abstract::Nuclear pore complexes (NPCs) provide the only sites for macromolecular transport between nucleus and cytoplasm. The nucleoporin p62, a component of higher eukaryotic NPCs, is located at the central gated channel and involved in nuclear trafficking of various cargos. p62 is organized into an N-terminal segment that co...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2006.04.007

    authors: Stochaj U,Bański P,Kodiha M,Matusiewicz N

    更新日期:2006-08-01 00:00:00

  • Analysis of the inductive effect of the genomic equivalent of HALF1 sequence in the reversion of rat dedifferentiated hepatoma cells.

    abstract::HALF1 (human activator of liver function 1) is a closed DNA duplex implicated in reversion of rat dedifferentiated C2 hepatoma cells to a well-differentiated state. A copy of HALF1 is found in high-molecular-weight DNA in the human genome. The genomic equivalent of HALF1 and its flanking sequences [gH(5'-3') fragment]...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1994.1180

    authors: Boccaccio C,Meunier-Rotival M,Deschatrette J

    更新日期:1994-07-01 00:00:00

  • ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/β-catenin signaling pathway.

    abstract::Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in China with a poor prognosis. Most ESCC patients were diagnosed at advanced stages, losing the opportunity for surgical excision. Hence, it remains a pressing work to identify biomarkers for early detection, prognosis prediction and target...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2018.03.017

    authors: Yuan H,Zhou W,Yang Y,Xue L,Liu L,Song Y

    更新日期:2018-06-01 00:00:00

  • Transfer of purine metabolites between cells through the medium and via cell contacts in cocultures of HGPRT+ and HGPRT- cells.

    abstract::Cells with and without hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity were used to examine the transfer of purine metabolites through the medium and via cell contacts. HGPRT- Chinese hamster and human fibroblasts were able to incorporate 3H-labeled purine metabolite(s) from medium in which mouse HGPRT...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/0014-4827(87)90346-6

    authors: Bols NC,Mosser DD,Boliska SA

    更新日期:1987-11-01 00:00:00

  • The antioxidant, rather than prooxidant, activities of quercetin on normal cells: quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis.

    abstract::The bioflavonoid quercetin is a dietary anticancer chemical that is capable of inducing apoptosis in tumor cells. Although the activity of quercetin is believed to be due to its antioxidative properties, it has recently been suggested that quercetin also has prooxidant activities, which might effect cytotoxicity direc...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/s0014-4827(03)00410-5

    authors: Lee JC,Kim J,Park JK,Chung GH,Jang YS

    更新日期:2003-12-10 00:00:00

  • Signaling interplay between PARP1 and ROS regulates stress-induced cell death and developmental changes in Dictyostelium discoideum.

    abstract::Poly (ADP-ribose) polymerase-1 (PARP1) is a DNA damage sensor that gets activated in proportion to the damage, helping cells to determine whether to repair the damage or initiate cell death processes. We have previously shown PARP1's significance in the developmental processes of Dictyostelium discoideum in addition t...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2020.112364

    authors: Mir H,Rajawat J,Vohra I,Vaishnav J,Kadam A,Begum R

    更新日期:2020-12-15 00:00:00

  • Elevated levels of polyamines alter chromatin in murine skin and tumors without global changes in nucleosome acetylation.

    abstract::Polyamines affect nucleosome oligomerization and DNA conformation in vitro, yet little information exists regarding the influence of naturally synthesized polyamines on mammalian chromatin. Capitalizing on the relative inefficiency of a moderate ionic strength extraction buffer to dissociate histones, we obtained evid...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/s0014-4827(03)00352-5

    authors: Hobbs CA,Paul BA,Gilmour SK

    更新日期:2003-11-01 00:00:00

  • 1,25-Dihydroxyvitamin D3 and Transforming Growth Factor-beta Act Synergistically to Override Extinction of LiversolidusBonesolidusKidney Alkaline Phosphatase in Osteosarcoma Hybrid Cells

    abstract::In this study, a somatic cell genetic approach was used to study the regulation of liversolidusbonesoliduskidney alkaline phosphatase (ALPL) gene expression in osteoblasts. ALPL plays an important role in skeletal mineralization and serves as a good index of bone formation. A series of intertypic hybrids constructed b...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:

    authors: Johnson-Pais TL,Leach RJ

    更新日期:1996-07-10 00:00:00

  • Immunofluorescent localization of histone H10 in the nuclei of proliferating and differentiating Friend cells.

    abstract::By using affinity-purified antibodies to H10 and to H1AB the localization of these histones was studied by indirect immunofluorescence in the nuclei of proliferating (EAT and uninduced Friend cells) and of differentiating (induced Friend cells) cell populations. While with H1AB antibodies a bright fluorescence all ove...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/0014-4827(88)90019-5

    authors: Banchev T,Srebreva L,Zlatanova J,Tsanev R

    更新日期:1988-07-01 00:00:00

  • Hydrogen peroxide lethality is associated with a decreased ability to maintain positive DNA supercoiling.

    abstract::Hydrogen peroxide is more toxic to mammalian cells at 37 degrees C than 0 degree C at all concentrations studied. Histone-free nuclei (nucleoids) extracted from treated cells have a reduced ability to maintain positive DNA supercoiling, with the maximum effect at the higher temperature. Prior exposure of cells to sodi...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/0014-4827(92)90088-p

    authors: Vaughan AT,Gordon DJ

    更新日期:1992-10-01 00:00:00

  • Control of apoptosis and growth of malignant T lymphoma cells by lymph node stromal cells.

    abstract::We have previously established the malignant T lymphoma CS-21 cell line from a spontaneous lymphoma in a BALB/c mouse. CS-21 lymphoma cells grew continuously when they were cocultured with stromal CA-12 cells prepared from lymph nodes. CS-21 lymphoma cells, however, could not proliferate by themselves, and they underw...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1993.1193

    authors: Kataoka S,Naito M,Fujita N,Ishii H,Ishii S,Yamori T,Nakajima M,Tsuruo T

    更新日期:1993-08-01 00:00:00

  • Tim-3 suppresses the killing effect of Vγ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression.

    abstract::Gamma delta (γδ) T cell-based tumor immunotherapy has been one of the most promising cancer immunotherapeutic strategies. However, the key regulators of the Vγ9Vδ2 T cell-mediated antitumor response remain unclear. Recently, mounting reports have indicated that Tim-3 performs critical roles in the regulation of the ac...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2019.111719

    authors: Li X,Lu H,Gu Y,Zhang X,Zhang G,Shi T,Chen W

    更新日期:2020-01-01 00:00:00

  • NLRP3 inflammasome inhibition attenuates cisplatin-induced renal fibrosis by decreasing oxidative stress and inflammation.

    abstract:BACKGROUND/AIMS:The NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome is involved in the progression of chronic kidney disease in several rodent models. Here, we investigated whether a specific inhibitor of NLRP3 inflammasome, MCC950, can attenuate cisplatin-induced renal fibrosis. MATERIALS:Renal fibr...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2019.07.001

    authors: Li S,Lin Q,Shao X,Mou S,Gu L,Wang L,Zhang Z,Shen J,Zhou Y,Qi C,Jin H,Pang H,Ni Z

    更新日期:2019-10-01 00:00:00

  • Scleroderma-derived human fibroblasts retain abnormal phenotypic and functional characteristics following retroviral transduction with the SV40 tsT antigen.

    abstract::In this study an amphotropic retrovirus has been used to efficiently transduce normal human (NF) and scleroderma (systemic sclerosis; SSc) dermal fibroblasts (SScF) with a sequence encoding a temperature-sensitive mutant of the SV40 large T antigen (tsA58-U19). From the primary outgrowths of skin explants, cultures we...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1995.1332

    authors: Xu S,Vancheeswaran R,Bou-Gharios G,O'Hare MJ,Olsen I,Abraham D,Black C

    更新日期:1995-10-01 00:00:00

  • Occurrence of proteinaceous 10-nm filaments throughout the cytoplasm of algae of the order Dasycladales.

    abstract::Previously, whole-mount electron microscopy of nuclei extruded together with residual cytoplasm from the rhizoids of several algal species of the order Dasycladales has revealed the occurrence of an intra- and perinuclear network of 10-nm filaments morphologically indistinguishable from that of mammalian vimentin inte...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1997.3924

    authors: Berger S,Wittke W,Traub P

    更新日期:1998-05-01 00:00:00

  • Active RB elicits late G1/S inhibition.

    abstract::The retinoblastoma tumor suppressor protein (RB) is activated/dephosphorylated to mediate cell cycle inhibition in response to antimitogenic signals. To elucidate the mode of RB action at this critical transition, we utilized cell lines that can be induced to express a constitutively active allele of RB (PSM-RB). As e...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.2002.5510

    authors: Angus SP,Fribourg AF,Markey MP,Williams SL,Horn HF,DeGregori J,Kowalik TF,Fukasawa K,Knudsen ES

    更新日期:2002-06-10 00:00:00

  • Recruitment of phosphorylated small heat shock protein Hsp27 to nuclear speckles without stress.

    abstract::During stress, the mammalian small heat shock protein Hsp27 enters cell nuclei. The present study examines the requirements for entry of Hsp27 into nuclei of normal rat kidney (NRK) renal epithelial cells, and for its interactions with specific nuclear structures. We find that phosphorylation of Hsp27 is necessary for...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2006.10.004

    authors: Bryantsev AL,Chechenova MB,Shelden EA

    更新日期:2007-01-01 00:00:00

  • Target proteins for arginine-specific mono(ADP-ribosyl) transferase in membrane fractions from chick skeletal muscle cells.

    abstract::In a previous study, we found that a specific inhibitor of cellular arginine-specific mono(ADP-ribosyl) transferase, meta-iodobenzylguanidine (MIBG), reversibly inhibited both proliferation and differentiation of cultured embryonic chick primary muscle myoblasts. In addition, we observed that arginine-specific ADP-rib...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1996.0213

    authors: Huang HY,Zhou H,Huiatt TW,Graves DJ

    更新日期:1996-07-10 00:00:00

  • Regulation of protrusion shape and adhesion to the substratum during chemotactic responses of mammalian carcinoma cells.

    abstract::We report here the first direct observation of chemotaxis to EGF by rat mammary carcinoma cells. When exposed to a gradient of EGF diffusing from a micropipette, MTLn3 cells displayed typical ameboid chemotaxis, extending a lamellipod-like protrusion and moving toward the pipette. Using a homogeneous upshift in EGF to...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1998.4031

    authors: Bailly M,Yan L,Whitesides GM,Condeelis JS,Segall JE

    更新日期:1998-06-15 00:00:00

  • Autophagy is involved in the differentiation of epicardial progenitor cells into vascular smooth muscle cells in mice.

    abstract::Most coronary smooth muscle cells(CoSMCs) are differentiated from epicardial progenitor cells(EPCs), but the specific mechanism is not fully investigated. Previous studies have shown that autophagy plays an important role for smooth muscle cells(SMCs) differentiation, yet whether autophagy is involved in the different...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2018.12.025

    authors: Liu Y,Liu B,Li Y,Li Y,Du J,Deng S,Jing X,She Q

    更新日期:2019-02-15 00:00:00

  • Collagen XIV and a related recombinant fragment protect human vascular smooth muscle cells from calcium-/phosphate-induced osteochondrocytic transdifferentiation.

    abstract::Transdifferentiation of vascular smooth muscle cells (VSMC) promotes the development of vascular calcifications such as arteriosclerosis. The aim was to investigate effects of specific extracellular matrix (ECM) components on transdifferentiation of VSMC to identify novel ECM-based therapeutic tools. Human collagens I...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2017.06.018

    authors: Freise C,Bobb V,Querfeld U

    更新日期:2017-09-15 00:00:00

  • Modulation of the phosphorylation of glucose-regulated protein, GRP78, by transformation and inhibition of glycosylation.

    abstract::The phosphorylation of glucose-regulated protein, GRP78, is thought to be involved in the regulation of the binding function of GRP78 to immunoglobulin heavy chains. The phosphorylation of GRP78 proceeded faster in transformed cells than in normal cells, whereas the levels of GRP78 synthesis and accumulation were simi...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1993.1060

    authors: Satoh M,Nakai A,Sokawa Y,Hirayoshi K,Nagata K

    更新日期:1993-03-01 00:00:00

  • Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices.

    abstract::Studies were carried out to test the idea that transforming growth factor beta (TGFbeta) stimulated fibroblast contraction of collagen matrices by different mechanisms depending on mechanical loading on the cells and matrix. Under mechanically unloaded conditions (floating matrices), TGFbeta stimulated contraction dir...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.2001.5445

    authors: Grinnell F,Ho CH

    更新日期:2002-02-15 00:00:00

  • Characterization of lamina-bound chromatin in the nuclear shell isolated from HeLa cells.

    abstract::The structure and the polypeptide composition of the nuclear shell isolated from interphase HeLa cells have been investigated and compared to those of the intranuclear material. The isolated nuclear shell contains chromatin superstructures (28-32 nm thick fibres) made of tightly packed nucleosomes that resist low ioni...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/0014-4827(85)90557-9

    authors: Bouvier D,Hubert J,Seve AP,Bouteille M

    更新日期:1985-02-01 00:00:00

  • In situ hybridization in living cells: detection of RNA molecules.

    abstract::Fluorescence hybridization is a widely used technique in cell biology and pathology for detecting specific nucleic acid (DNA and RNA) sequences in fixed cells. This technique does not, however, provide dynamic information on the intracellular behavior of the targeted molecules. The aim of this work was to investigate ...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1996.3464

    authors: Paillasson S,Van De Corput M,Dirks RW,Tanke HJ,Robert-Nicoud M,Ronot X

    更新日期:1997-02-25 00:00:00

  • Regulation of p53 in embryonic stem cells.

    abstract::Despite an increasing interest in the role of the p53 tumour suppressor protein in embryonic stem cells, not much is known about its regulation in this cell type. We show that the relatively high amount of p53 protein correlates with a higher amount of p53 RNA in ES cells compared to differentiated cells. Moreover, p5...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2010.06.006

    authors: Solozobova V,Blattner C

    更新日期:2010-09-10 00:00:00

  • Analysis of Tax-expressing cell lines generated from HTLV-I tax-transgenic mice: correlation between c-myc overexpression and neoplastic potential.

    abstract::Human T-cell leukemia/lymphotropic virus type I (HTLV-I) infection causes a variety of human diseases, including adult T-cell leukemia/lymphoma. The viral transactivator Tax has been implicated as a key factor in the HTLV-I-induced transformation pathway. To investigate the components of this pathway, we derived fibro...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1006/excr.1998.4381

    authors: Saggioro D,D'agostino DM,Chieco-Bianchi L

    更新日期:1999-03-15 00:00:00

  • A conserved peptide motif in Raver2 mediates its interaction with the polypyrimidine tract-binding protein.

    abstract::Raver2 was originally identified as a member of the hnRNP family through database searches revealing three N-terminal RNA recognition motifs (RRMs) bearing highest sequence identity in the RNP sequences to the related hnRNP Raver1. Outside the RRM region, both Raver proteins are quite divergent in sequence except for ...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/j.yexcr.2009.11.023

    authors: Henneberg B,Swiniarski S,Sabine Becke,Illenberger S

    更新日期:2010-04-01 00:00:00

  • The cytoplasmic pH, ATP content and total protein synthesis rate during heat-shock protein inducing treatments in yeast.

    abstract::In S. cerevisiae the induction of heat-shock protein (HSP) synthesis is accompanied by a decrease in the cytoplasmic and vacuolar pH as determined by means of [31P]NMR spectroscopy. The relationship of HSP synthesis and acidification of the cytoplasmic pH is dose-dependent under a variety of treatments (temperature in...

    journal_title:Experimental cell research

    pub_type: 杂志文章

    doi:10.1016/0014-4827(87)90117-0

    authors: Weitzel G,Pilatus U,Rensing L

    更新日期:1987-05-01 00:00:00