Abstract:
:PI3K was originally discovered as a lipid kinase involved in the phosphorylation of the inositol ring in position -3, leading to the synthesis of phosphatidyl-inositol-3-4 bisphosphate. The enzyme purified from rat liver is an heterodimer of two subunits of 85 and 110 KD respectively: it phosphorylates the D3 hydroxyl of phosphoinositides to produce phosphatidyl-inositol-3-phosphate. So far the function of the 3-phospho-inositide is unclear. It is likely that the entire phospholipid serves as a second messenger, since no phospholipase C has yet been found that can cleave the inositol group with a 3 phosphate residue. However the activation targets of this second messenger are still poorly known. Recently a novel/serine/theronine kinase was insolated by three groups and called differently RAC, PKB and AKT. It exhibits sequence homology with protein kinase A and C at the carboxyl terminal, whereas the aminoterminal domain has a plectrin homology. Activation of ATK is inhibited by wortmannin, a specific inhibitor of PI3K at very low concentrations. Furthermore inositol-3-phosphate can activate ATK in vitro. In addition very recently, a linkage of G-protein coupled receptors to the MAP kinase signalled pattern through PI3K has been discovered. But what is downstream of this pathway? 70S6 kinase is an attractive candidate since this kinase, involved in protein synthesis, is activated by AKT in vivo. Interestingly AKT is the cellular protooncogene of v-ATK and this implies that ATK induces a pathway of oncogenic transformation. AKT is inhibited by dominant negative mutants of ras and thus involved in the ras-raf-MAP kinase pathway. The role of PI3K is still indefinite but it must have a paramount importance in cell signalling since nearly all growth factor receptors recruit this enzyme and that the activity of fundamental growth factor receptors like PDGF, EGF and insulin are blocked by the specific inhibitor wortmannin, leading to the conclusion that the PI3K signal is much important in mitogenesis, protein synthesis, membrane ruffling, cell transformation and cell cycle progression.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Chiarugi Vdoi
10.1006/phrs.1997.0151subject
Has Abstractpub_date
1997-04-01 00:00:00pages
263-5issue
4eissn
1043-6618issn
1096-1186pii
S1043-6618(97)90151-1journal_volume
35pub_type
杂志文章abstract:OBJECTIVES:There is still a need to develop new effective medications for the treatment of ulcerative colitis, particularly for patients who are intolerant or resistant to first line therapies. This article compared the efficacy and safety of etrolizumab and infliximab in moderate to severe ulcerative colitis. METHODS...
journal_title:Pharmacological research
pub_type: 杂志文章,meta分析
doi:10.1016/j.phrs.2018.11.003
更新日期:2019-01-01 00:00:00
abstract::Sepsis induced myocardial dysfunction (SIMD) results in high morbidity and mortality. However, the effective therapeutic strategies for SIMD treatment remain limited. Sirt3 is the main mitochondrial Sirtuin member and is a key modulator of mitochondrial metabolism and function. In this study, we aimed to investigate t...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.104887
更新日期:2020-09-01 00:00:00
abstract::6-Mercaptopurine is a cytotoxic and immunosuppressant drug. The use of this drug is limited due to its poor bioavailability and short plasma half-life. In order to nullify these drawbacks, 6-mercaptopurine-chitosan nanoparticles (6-MP-CNPs) were prepared and evaluated to study the influence of preparation conditions o...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2015.07.025
更新日期:2015-10-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtai...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2017.09.001
更新日期:2017-11-01 00:00:00
abstract::This article summarizes the discovery and the development of endothelial biology with a special focus on the role of endothelium-dependent vasoconstriction. The physician-scientist Paul Michel Vanhoutte contributed many of the initial observations that helped to understand and form the main concepts of modern vascular...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2011.02.013
更新日期:2011-06-01 00:00:00
abstract::(+)-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine (3-PPP; a sigma receptor ligand), administered at 30 mg kg-1, 30 min before the test, significantly decreased the electroconvulsive threshold in mice, being ineffective in lower doses. 3-PPP (20 mg kg-1) diminished the protective activity of diphenylhydantoin, phenobarbi...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0548
更新日期:1999-12-01 00:00:00
abstract::Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolit...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2011.05.007
更新日期:2011-08-01 00:00:00
abstract::A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assess...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.07.018
更新日期:2016-09-01 00:00:00
abstract::Chronic stress can lead to depression due to elevated levels of stress hormones such as glucocorticoid. This is accompanied by an increase in reactive oxygen species (ROS) levels in the brain, which can cause dendritic spine loss and atrophy in neurons, followed by memory loss. Dicaffeoylquinic acids (diCQAs) are natu...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105252
更新日期:2020-11-01 00:00:00
abstract::N-acetyl penicillamine (NAP), a derivative of penicillamine and copper chelator has been employed as a potential protector of host stress organ injury during Plasmodium berghei infection in mice. Intramuscular injection of NAP (60 mg kg-1 body wt for 10 days) to P. berghei mice was able to restrict the hepato- and spl...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1997.0233
更新日期:1997-10-01 00:00:00
abstract::Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60-90%. So far the precise...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.1999.0535
更新日期:1999-10-01 00:00:00
abstract::Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2014.08.008
更新日期:2014-12-01 00:00:00
abstract::Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at the onset...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.11.029
更新日期:2017-03-01 00:00:00
abstract:AIM AND SCOPE:To determine the acute effects of increased intra-abdominal pressure (IAP) on the biochemistry, morphology, and contractility of the isolated terminal ileum of rats. BACKGROUND:Laparoscopic procedures are used clinically in diagnostic and treatment modalities and experimentally as a model of ischemia-rep...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.09.010
更新日期:2006-02-01 00:00:00
abstract::Atropine (5 mg/kg, s.c., twice daily) had no significant effect on 24-h water consumption on day 1 of treatment; on subsequent days the rats showed a significant increase. Procyclidine (5 mg/kg, s.c., twice daily) had a similar effect, except that the increase in daily water consumption began on the third day of treat...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(90)90745-y
更新日期:1990-01-01 00:00:00
abstract::Treatment of MC3T3E-1 osteoblast cultures with combined interferon- gamma(IFN- gamma), lipopolysaccharide (LPS) and tumor necrosis factor- alpha(TNF- alpha) induces expressions of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), resulting in sustained releases of large amounts of nitric oxide and IL-6....
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0778
更新日期:2001-03-01 00:00:00
abstract::The antioxidant properties of a novel water-soluble antioxidant of the benzofuran family (5-hydroxy-4,6,7-trimethyl-2,3-dihydrobenzofuran-2-acetic acid, BFA) were studied. In rat liver mitochondria BFA increases the lag-time and decreases the extent of lipid peroxidation induced by ascorbate/Fe2+; an IC50 value of abo...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(91)90041-u
更新日期:1991-12-01 00:00:00
abstract::Though the AMPA receptor has been implicated in several neurodegenerative processes (epilepsy, ischemia, spasticity), its role in cognition is yet to be clarified. The aim of this study was to assess in the rat the effects of the AMPA receptor antagonist NBQX (3.5, 7, 10, 20 and 30 mgkg(-1), i.p.) on learning and memo...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0898
更新日期:2002-01-01 00:00:00
abstract::The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104403
更新日期:2019-10-01 00:00:00
abstract::The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activiti...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0730
更新日期:2000-11-01 00:00:00
abstract::Regulatory T cells (Tregs) modulate ongoing immune responses to prevent autoimmunity in healthy bodies and inhibit effective anti-tumor immunity responses in tumor patients, leading to tumor progression. The function of Tregs in tumor immunity suggests that elimination of Tregs in the host may enhance the anti-tumor i...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.104659
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Thymidylate synthase (TS) expression levels appear to be related to response to 5-fluorouracil-(5-FU)-based chemotherapy in colorectal cancer (CRC) patients. Three polymorphisms have been proposed as modulators of TS expression: a tandemly repeated sequence (2R/3R) in the 5' UTR, a SNP (G>C) w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2011.04.006
更新日期:2011-09-01 00:00:00
abstract::Osteoporosis caused by aging and menopause had become an emerging threat to human health. The reduction of osteoblast differentiation has been considered to be an essential cause of osteoporosis. Osteoblast differentiation could be regulated by LncRNAs, and increasing evidences have proved that LncRNAs may be adopted ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105230
更新日期:2021-01-01 00:00:00
abstract::Aminoglycoside antibiotics are employed clinically because of their potent bactericidal activities, less bacterial resistance, post-antibiotic effects and low cost. However, drugs belong to this class are well-known to cause nephrotoxicity, which limits their frequent clinical exploitation. Gentamicin, a commonly used...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2010.04.004
更新日期:2010-09-01 00:00:00
abstract::As Traditional Chinese Medicine (TCM) transcends its cultural boundaries and becomes widely used in many countries around the world, one of the major risks to the growing use of TCM internationally is the damage caused to its reputation and to community safety when TCM practitioners are not adequately trained. Ensurin...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105217
更新日期:2020-11-01 00:00:00
abstract::This study was performed in order to investigate the cholinomimetic response of seminal vesicles isolated from rats treated with hydrocortisone acetate during perinatal life. At the adult phase, the body weight and the wet weight of the seminal vesicle of these animals were unchanged. However, these male rats exhibite...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Corticosteroids are shown to have deleterious effects on wound healing for various tissues. Arginine metabolism and nitric oxide (NO) synthesis play an important role in many aspects of inflammation and wound healing. The study was designed to evaluate the relationship of dexamethasone impaired healing of tracheal ana...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(02)00130-5
更新日期:2002-09-01 00:00:00
abstract::Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identifie...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.02.024
更新日期:2018-05-01 00:00:00
abstract::In the present study, an attempt has been made to elucidate the role of alpha 2-adrenoceptors in reserpine-induced emesis in pigeons. Reserpine was found to induce dose-dependent emesis and a 500 micrograms kg-1 dose was found to be the 100% emetic dose. alpha 2-adrenoceptor agonists clonidine and alpha-methylnoradren...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(94)80060-x
更新日期:1994-05-01 00:00:00
abstract::Local microcirculatory dysfunction within the pancreatic gland might be an important factor in the conversion of oedematous to necrotizing pancreatitis. Therapeutic agents, improving the pancreatic blood flow, might be valuable in acute pancreatitis treatment. An influence of nitric oxide, heparin and procaine treatme...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1997.0200
更新日期:1997-08-01 00:00:00