Abstract：
:Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates. The development of potent DPP4 inhibitors during the past two decades has led to the identification of DPP4 as a target in the treatment of type 2 diabetes. The favorable effect of DPP4 inhibitors is based on prevention of the in vivo inactivation of the incretin hormone, glucagon-like peptide-1 (GLP-1) by DPP4. Apart from GLP-1, a number of other biologically active peptides are truncated by DPP4. For these peptides, the physiological relevance of their truncation has yet to be fully elucidated. Within the last 10years, DPP4 inhibitors have been employed in several animal models of lung and heart disease, in which injury was induced by an ischemic insult followed by subsequent reperfusion. In this review, we present a state-of-the-art of the ischemia/reperfusion injury (IRI)-related pharmacological actions of DPP4 substrates, including GLP-1, stromal cell-derived factor-1 alpha and vasoactive intestinal peptide. Furthermore, we discuss the large body of experimental work that now provides compelling evidence for the advantageous impact of DPP4 targeting in IRI. However, possible risks as well as underlying mechanisms are yet to be elucidated before translating these promising treatment strategies into clinical practice.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Matheeussen V,Jungraithmayr W,De Meester Idoi
10.1016/j.pharmthera.2012.07.012subject
Has Abstractpub_date
2012-12-01 00:00:00pages
267-82issue
3eissn
0163-7258issn
1879-016Xpii
S0163-7258(12)00161-1journal_volume
136pub_type
杂志文章,评审abstract：:Changes in dNTP pools have been studied by a number of investigators, in a wide range of cell types. The in vitro pertubations in dNTP pool levels induced, in particular, by deoxynucleosides which act as allosteric modulators, are not totally consistent with current 'in vitro models' of ribonucleotide reductase functi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(85)90046-4
更新日期：1985-01-01 00:00:00
abstract：:During physiological development and after a stressor event, vascular cells communicate with each other to evoke new vessel formation-a process known as angiogenesis. This communication occurs via direct contact and via paracrine release of proteins and nucleic acids, both in a free form or encapsulated into micro-ves...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.10.001
更新日期：2017-03-01 00:00:00
abstract：:Enzymes of the UDP-glucuronosyltransferase (UGT) superfamily contribute to the elimination of drugs from almost all therapeutic classes. Awareness of the importance of glucuronidation as a drug clearance mechanism along with increased knowledge of the enzymology of drug and chemical metabolism has stimulated interest ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107689
更新日期：2021-02-01 00:00:00
abstract：:Several types of stem and progenitor cells are currently under investigation for their potential to accomplish vascular regeneration. This review focuses on embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We will discuss the technologies allowing for their derivation, culture expansion and main...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.10.004
更新日期：2011-01-01 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through de...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.01.003
更新日期：2008-04-01 00:00:00
abstract：:This article is a review of cyclic nucleotide phosphodiesterase(s) (CN PDE) from the point of view of the relationships between the newer aspects of the complex enzymology of CN PDE and recent major advances in CN PDE pharmacology. A consolidation of isozyme nomenclature to the proposed family designations is recommen...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90039-o
更新日期：1991-01-01 00:00:00
abstract：:We review the adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the small and large intestine. NSAIDs cause small intestinal inflammation in 65% of patients receiving the drugs long-term. The clinical implications of NSAID-induced enteropathy are that patients bleed and lose protein from the inflamma...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90008-6
更新日期：1994-04-01 00:00:00
abstract：:The mechanisms of monooxygenase induction and inhibition have been discussed from the standpoint of historic development, from the current concepts about the molecular mechanism of enzyme induction, and from the various possibilities by which inhibitors can interact with the complex cytochrome P-450 monooxygenase syst...
journal_title：Pharmacology & therapeutics
pub_type： 历史文章,杂志文章,评审
doi：10.1016/0163-7258(87)90020-9
更新日期：1987-01-01 00:00:00
abstract：:Long noncoding RNAs (lncRNAs) have multiple functions in the regulation of cellular homeostasis. In recent years, numerous studies have shown that tumor-associated lncRNAs play key roles in promoting and maintaining tumor initiation and progression by shaping the tumor microenvironment through changing tumor cell intr...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107591
更新日期：2020-09-01 00:00:00
abstract：:Preliminary investigations of the physical properties of oligonucleotide analogs that contain alternating methylphosphonate/phosphodiester linkages are described. An alternating oligo-2'-O-methylribonucleoside methylphosphonate, oligomer 1676, whose sequence is complementary to the upper hairpin region of human immuno...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00054-6
更新日期：2000-03-01 00:00:00
abstract：:The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tis...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.08.001
更新日期：2015-11-01 00:00:00
abstract：:This review concerns the development of small molecule therapeutics for the inherited neurodegenerative disease Friedreich ataxia (FRDA). FRDA is caused by transcriptional repression of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin and accompanying loss of frataxin protein. Frataxin insuf...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.06.014
更新日期：2007-11-01 00:00:00
abstract：:The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been exte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.09.003
更新日期：2019-02-01 00:00:00
abstract：:Several amphetamine analogs are potent psychostimulants and major drugs of abuse. In animal models, the psychomotor and reinforcing effects of amphetamine, methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), and methylphenidate (MPD; Ritalin) are thought to be dependent on increased extracellula...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.08.004
更新日期：2006-01-01 00:00:00
abstract：:The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient nutritional support to t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.06.006
更新日期：2015-09-01 00:00:00
abstract：:Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with hi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.004
更新日期：2018-06-01 00:00:00
abstract：:Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormo...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.09.004
更新日期：2009-01-01 00:00:00
abstract：:The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.04.005
更新日期：2008-07-01 00:00:00
abstract：:Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of c...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00048-6
更新日期：2000-08-01 00:00:00
abstract：:The neurobiological processes by which ethanol seeking and consumption are established and maintained are thought to involve areas of the brain that mediate motivated behavior, such as the mesolimbic dopamine system. The mesolimbic dopamine system is comprised of cells that originate in the ventral tegmental area (VTA...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.06.002
更新日期：2004-08-01 00:00:00
abstract：:Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.11.013
更新日期：2017-04-01 00:00:00
abstract：:Glucose-6-phospate dehydrogenase (G6PD) deficiency is estimated to affect more than 400 million people world-wide. This X-linked genetic deficiency puts stress on red blood cells (RBC), which may be further augmented under certain pathophysiological conditions and drug treatments. These conditions can cause hemolytic ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107788
更新日期：2020-12-14 00:00:00
abstract：:Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset o...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.11.006
更新日期：2006-05-01 00:00:00
abstract：:The association between vitamin D and multiple sclerosis has (re)-opened new interest in nutrition and natural compounds in the prevention and treatment of this neuroinflammatory disease. The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy,...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.11.015
更新日期：2015-04-01 00:00:00
abstract：:Cancer research has been focusing so far on genetic alterations in protein-coding genes. However, mounting evidence underlines the importance of epigenetic and post-transcriptional events in cancer progression and therapy resistance. Moreover, recent genome-wide studies show that disease-causing mutations and chromoso...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.04.001
更新日期：2018-09-01 00:00:00
abstract：:The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00013-8
更新日期：1998-08-01 00:00:00
abstract：:Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somatoautonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs such as cisplatin is associated with an increase in the co...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00057-3
更新日期：2003-08-01 00:00:00
abstract：:Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.10.011
更新日期：2019-03-01 00:00:00
abstract：:Since the first reports on chemokine function, much information has been generated on the implications of these molecules in numerous physiological and pathological processes, as well as on the signaling events activated through their binding to receptors. Despite these extensive studies, no chemokine-related drugs ha...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.05.002
更新日期：2011-09-01 00:00:00
abstract：:Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists s...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.09.003
更新日期：2012-01-01 00:00:00
