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 Pharmacoljournal_title
Biochemical pharmacologyauthors
Mattiolo P,Yuste VJ,Boix J,Ribas Jdoi
10.1016/j.bcp.2015.09.021subject
Has Abstractpub_date
2015-12-15 00:00:00pages
573-86issue
4eissn
0006-2952issn
1873-2968pii
S0006-2952(15)00631-0journal_volume
98pub_type
杂志文章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
更新日期:2013-12-15 00:00:00
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
更新日期:1997-05-09 00:00:00
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:
更新日期:1994-07-05 00:00:00
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
更新日期:2003-07-01 00:00:00
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
更新日期:2014-03-15 00:00:00
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
更新日期:1987-11-15 00:00:00
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
更新日期:1992-10-20 00:00:00
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
更新日期:2017-12-15 00:00:00
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
更新日期:1995-11-09 00:00:00
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
更新日期:1987-09-01 00:00:00
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
更新日期:1988-08-15 00:00:00
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
更新日期:2010-12-01 00:00:00
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
更新日期:2002-05-01 00:00:00
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
更新日期:2017-01-15 00:00:00
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
更新日期:1991-04-15 00:00:00
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
更新日期:2014-05-15 00:00:00
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
更新日期:2007-05-15 00:00:00
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
更新日期:1985-11-15 00:00:00
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
更新日期:1990-03-15 00:00:00
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
更新日期:2005-11-25 00:00:00
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
更新日期:2016-10-15 00:00:00
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
更新日期:2015-06-01 00:00:00
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
更新日期:1995-10-12 00:00:00
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
更新日期:2011-05-15 00:00:00
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
更新日期:1988-09-01 00:00:00
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
更新日期:1987-05-01 00:00:00
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
更新日期:1994-02-09 00:00:00
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
更新日期:1982-07-01 00:00:00
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
更新日期:2004-06-15 00:00:00
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
更新日期:1984-06-01 00:00:00