Autophagy exacerbates caspase-dependent apoptotic cell death after short times of starvation.

Abstract:

:Autophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and growth factors provoked cell death in a variety of cell lines. This death process was contingent upon caspase activation and was mediated by BAX/BAK proteins, thus indicating its apoptotic nature and the engagement of an intrinsic pathway. In order to abrogate autophagy, 3-methyladenine (3-MA), BECLIN-1 siRNA and Atg5 knock-out (Tet-Off type) approaches were alternatively employed. Irrespective of the procedure, at short times of starvation, we found that the ongoing autophagy was sensitizing cells to the permeabilization of the mitochondrial outer membrane (MOMP), caspase activation and, therefore, apoptosis. On the contrary, at longer times of starvation, autophagy displayed its characteristic pro-survival effect on cells. As far as we know, we provide the first experimental paradigm where time is the only variable determining the final outcome of autophagy. In other words, we have circumscribed in time the shift transforming autophagy from a cell death to a protection mechanism. Moreover, at short times, starvation-driven autophagy exacerbated the apoptotic cell death caused by several antitumor agents. In agreement with this fact, their apoptotic effects were greatly diminished by autophagy inhibition. The implications of these facts in tumor biology will be discussed.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Mattiolo P,Yuste VJ,Boix J,Ribas J

doi

10.1016/j.bcp.2015.09.021

subject

Has Abstract

pub_date

2015-12-15 00:00:00

pages

573-86

issue

4

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(15)00631-0

journal_volume

98

pub_type

杂志文章
  • Anti-fibrotic and anti-inflammatory properties of melatonin on human gingival fibroblasts in vitro.

    abstract::Melatonin (MEL) has been proposed as a therapeutic agent for the oral cavity, due to its antioxidant and anti-inflammatory effects since periodontal diseases are aggravated by free radicals, and by disproportionate immunological response to plaque microorganism. In addition, MEL promotes bone formation. This study aim...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2013.10.009

    authors: Gómez-Florit M,Ramis JM,Monjo M

    更新日期:2013-12-15 00:00:00

  • Differential regulation of expression of rat hippocampal muscarinic receptor subtypes following fimbria-fornix lesion.

    abstract::Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspirat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(97)00074-9

    authors: Zang Z,Creese I

    更新日期:1997-05-09 00:00:00

  • Vaninolol: a new selective beta 1-adrenoceptor antagonist derived from vanillin.

    abstract::The beta-adrenoceptor blocking properties of vaninolol ((+/-)4-[4'-(2-hydroxy-3-tert-butyl-aminopropoxy)-3'-methoxyphenyl]- 3-buten-2-one), derived from vanillin, were first investigated under in vivo and in vitro conditions. Vaninolol (0.1, 0.5, 1.0 mg/kg, i.v.), as well as propranolol, produced a dose-dependent brad...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:

    authors: Wu BN,Hwang TL,Liao CF,Chen IJ

    更新日期:1994-07-05 00:00:00

  • Cocaine-protein targets in mouse liver.

    abstract::Cocaine has been shown to be hepatotoxic in mice, rats and humans. N-Oxidative metabolism of cocaine is required for this effect, and it has been proposed that binding of cocaine reactive metabolites formed via this pathway might be responsible for cytotoxicity. To explore this hypothesis, cocaine-protein adducts in l...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(03)00246-6

    authors: Ndikum-Moffor FM,Roberts SM

    更新日期:2003-07-01 00:00:00

  • Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis.

    abstract::Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent ant...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2013.12.005

    authors: Tsai KL,Huang PH,Kao CL,Leu HB,Cheng YH,Liao YW,Yang YP,Chien Y,Wang CY,Hsiao CY,Chiou SH,Chen JW,Lin SJ

    更新日期:2014-03-15 00:00:00

  • Malotilate reduces collagen synthesis and cell migration activity of fibroblasts in vitro.

    abstract::Diisopropyl-1,3-dithiol-2-ylidenemalonate (malotilate) was studied for and compared with cyanidanol, hydrocortisone and colchicin on its impact on fibroblast cultures. Under in vitro conditions, malotilate specifically reduces collagen synthesis of fibroblasts. In addition, malotilate is an efficient inhibitor of fibr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(87)90464-3

    authors: Poeschl A,Rehn D,Dumont JM,Mueller PK,Hennings G

    更新日期:1987-11-15 00:00:00

  • Multiple effects of staurosporine, a kinase inhibitor, on thymocyte functions. Comparison with the effect of tyrosine kinase inhibitors.

    abstract::The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [3H]inositol incorporation into phospholipids were inhibited by staurosp...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(92)90473-v

    authors: Zilberman Y,Gutman Y

    更新日期:1992-10-20 00:00:00

  • The Ca2+/CaMKK2 axis mediates the telbivudine induced upregulation of creatine kinase: Implications for mechanism of antiviral nucleoside analogs' side effect.

    abstract::Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from creatine kinase (CK) elevation to myopathy. The purpose of this study was to explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on mitocho...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2017.10.005

    authors: Jianfei L,Min W,Chunlai M,Bicui C,Jiming Z,Bin W

    更新日期:2017-12-15 00:00:00

  • Production of adenosine and nucleoside analogs by the exchange reaction catalyzed by rat liver adenosine kinase.

    abstract::We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the absence of ATP, by an exchange reaction. In this study, we investigated whether Ado or AMP could be replaced in this exchange reaction by other nucleosides or...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(95)02033-0

    authors: Mimouni M,Bontemps F,Van den Berghe G

    更新日期:1995-11-09 00:00:00

  • Functional heterogeneity of vascular endothelial cells.

    abstract::This review has highlighted some of the well-described differences in endothelial cells derived from different sites of the vascular tree. In presenting a select group of endothelial properties, there was no intention to imply that these are the only properties of endothelial cells that exhibit heterogeneity. Nonethel...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/0006-2952(87)90252-8

    authors: Gerritsen ME

    更新日期:1987-09-01 00:00:00

  • Stimulation of cadmium uptake by estradiol in the kidney of male rats treated with cadmium.

    abstract::The present study was carried out to analyze the sex differences in the retention of Cd in rats treated with a small amount of Cd, and its mechanisms. Cd and Zn concentrations in the kidney and liver of female rats treated with 28 nmol Cd or 1 nmole Zn were significantly higher than those in male rats. Pretreatment wi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90305-x

    authors: Nishiyama S,Onosaka S,Taguchi T,Konishi Y,Tanaka K,Kinebuchi H

    更新日期:1988-08-15 00:00:00

  • Direct fusion of subunits of heterodimeric nitric oxide sensitive guanylyl cyclase leads to functional enzymes with preserved biochemical properties: evidence for isoform specific activation by ciguates.

    abstract::Nitric oxide sensitive guanylyl cyclase (NOsGC) is a heterodimeric enzyme consisting of an α and a β subunit. Two heterodimeric enzymes are known to be important for NO-signalling in humans: α(1)/β(1) and α(2)/β(1). No difference had so far been detected with respect to their pharmacological properties, but as we show...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2010.08.007

    authors: Haase N,Haase T,Kraehling JR,Behrends S

    更新日期:2010-12-01 00:00:00

  • Analysis of C-terminally substituted tachykinin-like peptide agonists by means of aequorin-based luminescent assays for human and insect neurokinin receptors.

    abstract::Aequorin-based assays for stable fly, Stomoxys calcitrans, (STKR) and human (neurokinin receptor 1 (NK1), neurokinin receptor 2 (NK2)) neurokinin-like receptors were employed to investigate the impact of a C-terminal amino acid exchange in synthetic vertebrate ('FXGLMa') and invertebrate ('FX1GX2Ra') tachykinin-like p...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(02)00914-0

    authors: Torfs H,Detheux M,Oonk HB,Akerman KE,Poels J,Van Loy T,De Loof A,Vassart G,Parmentier M,Vanden Broeck J

    更新日期:2002-05-01 00:00:00

  • Role of the endocannabinoid system in the control of mouse myometrium contractility during the menstrual cycle.

    abstract::Cannabis and cannabinoids are known to affect female reproduction. However, the role of the endocannabinoid system in mouse uterine contractility in the dioestrus and oestrus phases has not been previously investigated. The present study aimed at filling this gap. Endocannabinoid (anandamide and 2-arachidonoylglycerol...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2016.11.023

    authors: Pagano E,Orlando P,Finizio S,Rossi A,Buono L,Iannotti FA,Piscitelli F,Izzo AA,Di Marzo V,Borrelli F

    更新日期:2017-01-15 00:00:00

  • Interactions of 5-hydroxytryptamine with oxidative enzymes.

    abstract::Peroxidase (EC 1.11.1.7)/H2O2, ceruloplasmin (human type X)/O2, and tyrosinase (EC 1.14.18.1)/O2 all oxidized the indolic neurotransmitter 5-hydroxytryptamine (5-HT) in the physiological pH domain. Peroxidase/H2O2 oxidized 5-HT at pH values down to about 2.5. All oxidation reactions generated complex mixtures of produ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(91)90653-m

    authors: Wrona MZ,Dryhurst G

    更新日期:1991-04-15 00:00:00

  • Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    abstract::Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-C...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2014.02.008

    authors: Klint JK,Berecki G,Durek T,Mobli M,Knapp O,King GF,Adams DJ,Alewood PF,Rash LD

    更新日期:2014-05-15 00:00:00

  • The synergistic interaction of gemcitabine and cytosine arabinoside with the ribonucleotide reductase inhibitor triapine is schedule dependent.

    abstract::Gemcitabine and ara-C have multiple mechanisms of action: DNA incorporation and for gemcitabine also ribonucleotide reductase (RNR) inhibition. Since dCTP competes with their incorporation into DNA, dCTP depletion can potentiate their cytotoxicity. We investigated whether additional RNR inhibition by Triapine (3-AP), ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2007.01.025

    authors: Sigmond J,Kamphuis JA,Laan AC,Hoebe EK,Bergman AM,Peters GJ

    更新日期:2007-05-15 00:00:00

  • Role of adenosine uptake and metabolism by blood cells in the antiplatelet actions of dipyridamole, dilazep and nitrobenzylthioinosine.

    abstract::Adenosine (Ado, 10 microM) did not inhibit ADP-induced human platelet aggregation in whole blood. However, if the blood was preincubated with dipyridamole (10 microM), a potent inhibitor of the erythrocytic nucleoside transport system (NTS), Ado acted as a strong inhibitor of platelet aggregation. Similarly, Ado inhib...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90373-9

    authors: Dawicki DD,Agarwal KC,Parks RE Jr

    更新日期:1985-11-15 00:00:00

  • Bioactivation of N-arylhydroxamic acids by rat hepatic N-acetyltransferase. Detection of multiple enzyme forms by mechanism-based inactivation.

    abstract::Enzymatic N,O-acyltransfer of carcinogenic N-arylhydroxamic acids such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) results in the production of reactive electrophiles that can bond covalently with nucleophiles and also can cause inactivation of acyltransferase activity in a mechanism-based manner. Incubation of part...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(90)90277-r

    authors: Wick MJ,Hanna PE

    更新日期:1990-03-15 00:00:00

  • Pharmacological characterization of novel adenosine ligands in recombinant and native human A2B receptors.

    abstract::The present study was designed to evaluate the effects of novel and recognised compounds at human recombinant A(2B) adenosine receptors expressed in Chinese hamster ovary (hA(2B)CHO), in human embryonic kidney 293 (hA(2B)HEK-293) and at endogenous A(2B) receptors in human mast cells (HMC-1). Saturation binding experim...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2005.08.018

    authors: Varani K,Gessi S,Merighi S,Vincenzi F,Cattabriga E,Benini A,Klotz KN,Baraldi PG,Tabrizi MA,Lennan SM,Leung E,Borea PA

    更新日期:2005-11-25 00:00:00

  • Kinetic binding and activation profiles of endogenous tachykinins targeting the NK1 receptor.

    abstract::Ligand-receptor binding kinetics (i.e. association and dissociation rates) are emerging as important parameters for drug efficacy in vivo. Awareness of the kinetic behavior of endogenous ligands is pivotal, as drugs often have to compete with those. The binding kinetics of neurokinin 1 (NK1) receptor antagonists have ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2016.08.004

    authors: Nederpelt I,Bleeker D,Tuijt B,IJzerman AP,Heitman LH

    更新日期:2016-10-15 00:00:00

  • Development and mechanism investigation of a new piperlongumine derivative as a potent anti-inflammatory agent.

    abstract::Inflammation, especially chronic inflammation, is directly involvement in the pathogenesis of many diseases including cancer. An effective approach for managing inflammation is to employ chemicals to block activation of nuclear factor-κB (NF-κB), a key regulator for inflammatory processes. Piperlongumine (piplartine, ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2015.03.014

    authors: Sun LD,Wang F,Dai F,Wang YH,Lin D,Zhou B

    更新日期:2015-06-01 00:00:00

  • Effect of food intake on the activity of liver enzymes in partially hepatectomized rats treated with tumor necrosis factor.

    abstract::After partial hepatectomy (PHx), there are significant changes in the activity of a number of enzymes in the regenerating rat liver. Administration of low doses of recombinant human tumor necrosis factor-alpha (rHu-TNF) to normal rats induces similar changes in some of the enzymes but not in others. Because certain ob...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(95)00265-2

    authors: Yasmineh WG,Beyer HS,Caspers JI,Theologides A

    更新日期:1995-10-12 00:00:00

  • Cudratricusxanthone G inhibits human colorectal carcinoma cell invasion by MMP-2 down-regulation through suppressing activator protein-1 activity.

    abstract::Cudratricusxanthone G (CTXG), a natural bioactive cudratricusxanthone extracted from C. tricuspidata, has shown anti-cancer properties. However, the function and mechanism of CTXG in tumor invasion have not been elucidated to date. In this study, we investigated the inhibitory effect of CTXG on the proliferation, migr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2011.02.017

    authors: Kuang L,Wang L,Wang Q,Zhao Q,Du B,Li D,Luo J,Liu M,Hou A,Qian M

    更新日期:2011-05-15 00:00:00

  • Displacement of the bidentate malonate ligand from (d,l-trans-1,2-diaminocyclohexane)malonatoplatinum(II) by physiologically important compounds in vitro.

    abstract::Previous studies of platinum(II) compounds with bidentate leaving ligands have emphasized the contrast between the stability of the bidentate leaving ligand in vitro (T1/2 greater than 11 days in water) and the apparent reactivity of these bidentate platinum compounds in vivo. However, none of these studies actually m...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90646-6

    authors: Mauldin SK,Plescia M,Richard FA,Wyrick SD,Voyksner RD,Chaney SG

    更新日期:1988-09-01 00:00:00

  • Neurotoxic esterase: characterization of the solubilized enzyme and the conditions for its solubilization from chicken brain microsomal membranes with ionic, zwitterionic, or nonionic detergents.

    abstract::Neurotoxic esterase (NTE) is a membrane-bound protein found in highest concentration in brain and lymphocytes. The enzyme has no known physiological function, but its organophosphorylation and aging in neural tissue are thought to trigger the pathogenesis of organophosphorus-induced delayed neuropathy (OPIDN). Solubil...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(87)90104-3

    authors: Davis CS,Richardson RJ

    更新日期:1987-05-01 00:00:00

  • Cetaben and fibrates both influence the activities of peroxisomal enzymes in different ways.

    abstract::The effects of cetaben and clofibric acid were compared on the activities of peroxisomal enzymes in the liver and kidney of male Wistar rats. Cetaben at 200 mg/kg body wt increased the activities of all of the enzymes in the liver that were studied two to eight times, whereas the changes induced by the same dose of cl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90183-x

    authors: Chandoga J,Rojeková I,Hampl L,Hocman G

    更新日期:1994-02-09 00:00:00

  • Effect of disodium cromoglycate and cyclic AMP-active drugs on cytotoxic histamine release from rat mast cells.

    abstract::Disodium cromoglycate and compounds which elevated levels of cyclic AMP in the mast cell variously inhibited cytotoxic histamine release induced by the surface active agents melittin, Tween 20 and Triton X-100. These results are inconsistent with the postulated effects of the drugs on receptor mediated calcium channel...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90109-5

    authors: Pearce FL,Clements J

    更新日期:1982-07-01 00:00:00

  • The cystic fibrosis mutation G1349D within the signature motif LSHGH of NBD2 abolishes the activation of CFTR chloride channels by genistein.

    abstract::Cystic fibrosis (CF) is a common lethal genetic disease caused by autosomal recessive mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that belongs to the ATP-Binding Cassette (ABC) family of transporters. The class III CF mutations G551D and G1349D are located within the "s...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2004.02.022

    authors: Melin P,Thoreau V,Norez C,Bilan F,Kitzis A,Becq F

    更新日期:2004-06-15 00:00:00

  • Repeated administration of N-methyl-4-phenyl 1,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurones.

    abstract::N-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ( MPTP ) (10 mg/kg/day i.p.) was administered to rats for 16 days, which were then observed for a further 9-11 days. MPTP administration did not alter spontaneous locomotor activity or amphetamine (2.5 mg/kg ip)-induced locomotion. Apomorphine (0.25 mg/kg sc) did not alter ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90344-7

    authors: Boyce S,Kelly E,Reavill C,Jenner P,Marsden CD

    更新日期:1984-06-01 00:00:00