Involvement of ERK1/2 Kinase in Insulin-and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation

Isenović, Esma R.; Kedees, Mamdouh H.; Haidara, Mohamed A; Trpković, Ana; Mikhailidis, Dimitri P.; Marché, P.

doi:10.1177/0003319709358693

Cited by 29 publications

(26 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MEK1/2-ERK1/2 activation has been linked to mechanical stimulation-induced proliferation in diverse cell types, including chondrocytes (13,24,32). MEK1/2 activated ERK1/2, which functions as a final effector of signal transduction pathways and plays an essential role in cell proliferation, differentiation, and migration by directly activating transcription factors in the cytoplasm and nucleus (6,7,33). Ryan et al (9) reported that cyclic mechanical compression of articular cartilage induces chondrocyte proliferation by activation of the ERK1/2 pathway.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

Huang

Liang

Liu

et al. 2011

Braz J Med Biol Res

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…MEK1/2 and ERK1/2 exist in virtually all eukaryotic cells and control fundamental cellular functions (6)(7)(8). There is increasing evidence that MEK and ERK1/2 are involved in the regulation of chondrocyte proliferation, matrix synthesis, and migration in response to periodic mechanical stimulation (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

Huang

Liang

Liu

et al. 2011

Braz J Med Biol Res

View full text Add to dashboard Cite

“…A high level of insulin can hyper activate this pathway leading to Warburg 543 effect and cancer (154). Insulin and thrombin are known to produce VSMC proliferation (155). It is 544 well known that IGF produce proliferation of SMC (156)(157)(158)(159).In this context one can see Insulin 545…”

Section: B) 526mentioning

confidence: 99%

Fundamental role of Warburg effect in various pathophysiological processes

Natesan¹

2017

Preprint

View full text Add to dashboard Cite

Even though high NO via iNOS was involved in most of the pathologies including sepsis, any 56 substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect 57 and irreversible dedifferentiation. A mild and reversible Warburg differentiation dedifferentiation 58 effect may be necessary for normal functioning and the same effect in exaggerated and irreversible 59 way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the 60 diseases including septic shock. 61 62 Keywords: Septic shock, Warburg effect, dedifferentiation, differentiation therapy, ascorbic acid, 63 adrenergic blockers, glycolysis. 64Abbreviations : systemic hypertension(SHT), pulmonary arterial hypertension (PAH),congestive 65 heart failure (CHF), acute kidney injury(AKI),acute respiratory distress syndrome(ARDS),diabetes 66 mellitus(DM),inducible nitric oxide synthase (iNOS) . 67 68 69 70 INTRODUCTION: 71This review article tries to show the fundamental role played by Warburg effect in most of the 72 pathologies. Warburg common pathogenesis model is proposed to show the common underlying 73 mechanism in most of the pathologies and septic shock was used as the base model. 74Sepsis is the harmful systemic response of the host to the infection (1). According to Lewis Thomas 75 the host's response to pathogen is more detrimental than the pathogen itself (2). Septic shock and 76 severe sepsis associated multi-organ dysfunction carries high mortality rate ~ 40 -70% (3,4). 77Septic shock is refractory to the vasopressors in most of the cases; this includes norepinephrine, the 78 primary drug used in reviving blood pressure in septic shock. Vascular hypo reactivity to various 79 vasopressors in septic shock has been studied extensively, many reviews are available (5,86). 80Irrespective of advances in this field, exact underlying mechanism behind septic shock is still a 81 mystery. Post mortem studies couldn't find the underlying cause in most of the cases, surprisingly 82 most of the organs looked normal (6).Lot of treatment options which were successful in animal 83 models were failed to show benefit in human studies, ranging from Nitric oxide Synthase (NOS) 84Inhibitors, Cyclooxygenase (COX) Inhibitors, endotoxin neutralizing proteins, TNF alpha 85 antagonists etc.., (3). Some of the recent promising directions include, counterintuitive use of 86 antihypertensive in septic shock -alpha2 adrenergic receptor agonists -clonidine (7-9), beta 87 blockers reviewed in (10, 11) -aimed to reduce the sympathetic hyper activation and hyper 88 metabolism associated with sepsis. Alpha2 AR antagonist also has been shown to improve survival 89 in sepsis animal model (12). Vitamin C has been used in sepsis reviewed in (13), Glycolysis 90 inhibitor shikonin (14), cytochrome C (15) and Caffeine (16). 91 Warburg common pathogenesis model has been proposed in this review article to explain the role of 92Warburg effect in most of the pathologies using septic shock as the base model. The model was 9...

show abstract

“…More than half of the drugs currently in clinical use target GPCR by either mimicking endogenous GPCR ligands, blocking ligand access to the receptor or by modulating ligand production [14], which also represents the mechanism of action of sympatholytic and sympathomimetic drugs. Agonist-dependent desensitization of GPCR is caused by the phosphorylation of the specific receptor by the GRK family [15][16][17][18]. GRKs have a central catalytic domain flanked by amino-terminal and carboxyl-terminal domains which contain specific regulatory sites (Figure 1) [10].…”

Section: G Protein Related Kinases -General Overviewmentioning

confidence: 99%

State of the art paper The role of G protein coupled receptor kinases in neurocardiovascular pathophysiology

Bojić¹,

Sudar-Milovanović²,

Mikhailidis³

et al. 2012

aoms

View full text Add to dashboard Cite

A b s t r a c tIn coronary artery disease the G protein related kinases (GRKs) play a role in desensitization of β-adrenoreceptors (AR) after coronary occlusion. Targeted deletion and lowering of cardiac myocyte GRK-2 decreases the risk of postischemic heart failure (HF). Studies carried out in humans confirm the role of GRK-2 as a marker for the progression of HF after myocardial infarction (MI). The level of GRK-2 could be an indicator of β-AR blocker efficacy in patients with acute coronary syndrome. Elevated levels of GRK-2 are an early ubiquitous consequence of myocardial injury. In hypertension an increased level of GRK-2 was reported in both animal models and human studies. The role of GRKs in vagally mediated disorders such as vasovagal syncope and atrial fibrillation remains controversial. The role of GRKs in the pathogenesis of neurocardiological diseases provides an insight into the molecular pathogenesis process, opens potential therapeutic options and suggests new directions for scientific research.K Ke ey y w wo or rd ds s: : autonomic, sympathetic, vagal, molecular signaling pathway. Neurocardiovascular pathophysiology: sympathetic versus vagally mediated disordersNeural control of the cardiovascular (CV) system is an integral part of CV physiology and consequently a part of CV pathological mechanisms. Two fundamental parts of the autonomic nervous system -the sympathetic and parasympathetic (vagal) components -play a role in the development and initiation of the pathological process. The classification of neurocardiological disorders by Goldstein [1] is as follows: 1) Sympathetic disorders -diseases in which activation of the catecholamine system worsens an independent pathological state (coronary artery disease, arrhythmias as long QT syndrome, sudden death, heart failure (HF)) as well as diseases in which abnormal catecholaminergic function is etiologic (sympathetic neurocirculatory failure, hypertension, cardiac necrosis and cardiomyopathy), and 2) Vagally mediated disorders -both neurally mediated syncope (vasovagal syncope, carotid sinus hypersensitivity) and vagally mediated atrial fibrillation. Neural regulation of the CV system can be studied by using different techniques [2][3][4][5][6][7][8]. G protein related kinases (GRKs) exist in 7 isoforms -GRK 1-7. They are serine-threonine protein kinases that are C Co or rr re es sp po on nd di in ng g a au ut th ho or r: :

show abstract

Involvement of ERK1/2 Kinase in Insulin-and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation

Cited by 29 publications

References 64 publications

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

Fundamental role of Warburg effect in various pathophysiological processes

State of the art paper The role of G protein coupled receptor kinases in neurocardiovascular pathophysiology

Contact Info

Product

Resources

About