Systems biology of the metabolic network regulated by the Akt pathway

Mosca, Ettore; Barcella, Matteo; Alfieri, Roberta; Bevilacqua, Annamaria; Canti, Gianfranco; Milanesi, Luciano

doi:10.1016/j.biotechadv.2011.08.004

Cited by 37 publications

(29 citation statements)

References 89 publications

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“…It is important to understand the roles of these different mechanisms in disease context. As more and more cross-talk between Akt and other signal transduction pathways becomes evident, more research should focus on the system biology of these pathways [182]. Moreover, cardiovascular system consists of several types of tissues in a unique arrangement.…”

Section: Future Perspectivesmentioning

confidence: 99%

The critical role of Akt in cardiovascular function

Abeyrathna

2015

Vascular Pharmacology

336

222

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Akt kinase, a member of AGC kinases, is important in many cellular functions including proliferation, migration, cell growth and metabolism. There are three known Akt isoforms which play critical and diverse roles in the cardiovascular system. Akt activity is regulated by its upstream regulatory pathways at transcriptional and post-translational levels. beta-catenin/Tcf-4, GLI1 and Stat-3 are some of few known transcriptional regulators of AKT gene. Threonine 308 and serine 473 are the two critical phosphorylation sites of Akt1. Translocation of Akt to the cell membrane facilitates PDK1 phosphorylation of the threonine site. The serine site is phosphorylated by mTORC2. Ack1, Src, PTK6, TBK1, IKBKE and IKKε are some of the non-canonical pathways which affect the Akt activity. Protein-protein interactions of Akt to actin and Hsp90 increase the Akt activity while Akt binding to other proteins such as CTMP and TRB3 reduces the Akt activity. The action of Akt on its downstream targets determines its function in cardiovascular processes such as cell survival, growth, proliferation, angiogenesis, vasorelaxation, and cell metabolism. Akt promotes cell survival via caspase-9, YAP, Bcl-2, and Bcl-x activities. Inhibition of FoxO proteins by Akt also increases cell survival by transcriptional mechanisms. Akt stimulates cell growth and proliferation through mTORC1. Akt also increases VEGF secretion and mediates eNOS phosphorylation, vasorelaxation and angiogenesis. Akt can increase cellular metabolism through its downstream targets GSK3 and GLUT4. The alterations of Akt signaling play an important role in many cardiovascular pathological processes such as atherosclerosis, cardiac hypertrophy, and vascular remodeling. Several Akt inhibitors have been developed and tested as anti-tumor agents. They could be potential novel therapeutics for the cardiovascular diseases.

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Section: Future Perspectivesmentioning

confidence: 99%

The critical role of Akt in cardiovascular function

Abeyrathna

2015

Vascular Pharmacology

336

222

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“…PI3K/Akt signaling participates in multiple cellular metabolic pathways, particularly in cellular energy metabolism. 46 Akt is the key signaling molecule in cell survival, proliferation, growth, and differentiation, and is involved in angiogenesis through the pro-survival function of VEGF. 47 Moreover, Akt phosphorylation is an important event in regulating the survival of growth factors such as VEGF, transcription factors such as HIF-1α, and oncogenes.…”

Section: Discussionmentioning

confidence: 99%

Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation

Jang¹,

Park²,

Rim³

et al. 2012

IJN

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Abstract:The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.

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“…Mitogens and growth factors bind to the growth factor receptors, activate the associated tyrosine kinase which subsequently activates phosphoinositide 3 (PIP3)-kinase (PI3K). PI3K activates protein kinase B (AKT) (Mosca et al, 2011). In particular, PI3K/AKT stimulates expression of the glucose transporter 1 (GLUT1), hexokinase (HK-1), and phosphofructokinase (PFK-1).…”

Section: Regulation Of Metabolic Reactions In Mammalian Cellsmentioning

confidence: 99%

Metabolic host responses to infection by intracellular bacterial pathogens

Eisenreich¹,

Heesemann²,

Rudel³

et al. 2013

Front. Cell. Infect. Microbiol.

168

150

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The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies.

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Systems biology of the metabolic network regulated by the Akt pathway

Cited by 37 publications

References 89 publications

The critical role of Akt in cardiovascular function

The critical role of Akt in cardiovascular function

Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation

Metabolic host responses to infection by intracellular bacterial pathogens

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