Phosphatidylinositol 3-Kinase

Sata, Masataka; Nagai, Ryozo

doi:10.1161/01.res.0000031956.29928.62

Cited by 34 publications

(12 citation statements)

References 29 publications

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“…In summary, earlier studies have indicated that activation of the PI3K/Akt pathway in adult VSMC is involved in controlling growth and cell survival (53). Our data provide novel findings that this pathway also controls the phenotype of these cells through direct effects on SM-specific transcription.…”

Section: Akt Mediates Suppression Of Sm Gene Expression-tosupporting

confidence: 67%

Platelet-derived Growth Factor-BB-mediated Activation of Akt Suppresses Smooth Muscle-specific Gene Expression through Inhibition of Mitogen-activated Protein Kinase and Redistribution of Serum Response Factor

Kaplan-Albuquerque

Garat

Desseva

et al. 2003

Journal of Biological Chemistry

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Platelet-derived growth factor (PDGF) inhibits expression of smooth muscle (SM) genes in vascular smooth muscle cells and blocks induction by arginine vasopressin (AVP). We have previously demonstrated that suppression of SM-␣-actin by PDGF-BB is mediated in part through a Ras-dependent pathway. This study examined the role of phosphatidylinositol 3-kinase (PI3K)y and its downstream effector, Akt, in regulating SM gene expression. PDGF caused a rapid sustained activation of Akt, whereas AVP caused only a small transient increase. PDGF selectively caused a sustained stimulation of p85/p110␣ PI3K. In contrast, p85/110␤ PI3K activity was not altered by either PDGF or AVP, whereas both agents caused a delayed activation of Class IB p101/110␥ PI3K. Expression of a gain-of-function PI3K or myristoylated Akt (myr-Akt) mimicked the inhibitory effect of PDGF on SM-␣-actin and SM22␣ expression. Pretreatment with LY 294002 reversed the inhibitory effect of PDGF. Expression of myr-Akt selectively inhibited AVP-induced activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinases, which we have shown are critical for induction of these genes. Nuclear extracts from PDGF-stimulated or myr-Akt expressing cells showed reduced serum response factor binding to SM-specific CArG elements. This was associated with appearance of serum response factor in the cytoplasm. These data indicate that activation of p85/p110␣/Akt mediates suppression of SM gene expression by PDGF.

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Section: Akt Mediates Suppression Of Sm Gene Expression-tosupporting

confidence: 67%

Platelet-derived Growth Factor-BB-mediated Activation of Akt Suppresses Smooth Muscle-specific Gene Expression through Inhibition of Mitogen-activated Protein Kinase and Redistribution of Serum Response Factor

Kaplan-Albuquerque

Garat

Desseva

et al. 2003

Journal of Biological Chemistry

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“…PI3K, which is activated by upstream p-IRS1 (tyr989), upregulates its downstream target (Akt phosphorylation). PI3K exhibits its effects by translocating to the cell membrane from the cytoplasm [32, 33]. Our study found that the level of cell membrane PI3Kp85 (m-PI3Kp85) in the CPAE group was significantly higher than in the control group (Figure 5(c)).…”

Section: Resultsmentioning

confidence: 84%

Cyclocarya paliurus (Batal.) Ijinskaja Aqueous Extract (CPAE) Ameliorates Obesity by Improving Insulin Signaling in the Hypothalamus of a Metabolic Syndrome Rat Model

Yoshitomi

Sun

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Background Antiobesity drugs may not be optimal for treating obesity. However novel antiobesity agents, especially those derived from natural products, may be suitable. Therefore, we investigated the effects and mechanisms of Cyclocarya paliurus (CP) aqueous extract (CPAE) on obesity. Methods SHR.Cg-Leprcp/NDmcr (SHR/cp) rats were used as a model of obesity and metabolic syndrome. Experimental animals were allocated into two groups—control and CPAE (0.5 g/kg)—for a 7-week treatment period. Examinations were performed, including general physiological characteristics, obesity-related biochemical parameters, and insulin-signaling pathway-related proteins in the hypothalamus. Results Treatment with CPAE reduced food intake, body weight, organ weight, fat mass, and body mass index (BMI) in SHR/cp rats. Meanwhile, CPAE also decreased the levels of fasting serum glucose, fasting serum insulin, HOMA-IR, serum free fatty acids, serum malondialdehyde, serum superoxide dismutase, and serum total-glutathione. The levels of phosphorylation of target proteins—including InsR, IRS1, PI3Kp85, Akt, and FoXO1 as well as protein expression of POMC—were significantly upregulated in the hypothalamus, but NPY expression remarkably decreased. Conclusions CPAE has antiobesity, antihypoglycemic, antihypolipidemic, and antioxidant properties. The mechanism responsible for the antiobesity effect of CPAE may be related to suppression of energy intake via regulation of insulin-signaling pathway in the hypothalamus.

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“…PI3K/Akt is involved in both cytosolic and nuclear signaling in endothelial cell where it regulates vascular homeostasis and angiogenesis [30], [31]. PI3K signaling mediates Akt/PKB phosphorylates eNOS at serine-1177 residue [32]–[34].…”

Section: Discussionmentioning

confidence: 99%

The Transcriptional Response in Human Umbilical Vein Endothelial Cells Exposed to Insulin: A Dynamic Gene Expression Approach

et al. 2010

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BackgroundIn diabetes chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation through the activation of the MAP kinases, which in turn regulate cellular proliferation. However, it is not known whether insulin itself could increase the transcription of specific genes for cellular proliferation in the endothelium. Hence, the characterization of transcriptional modifications in endothelium is an important step for a better understanding of the mechanism of insulin action and the relationship between endothelial cell dysfunction and insulin resistance.Methodology and principal findingsThe transcriptional response of endothelial cells in the 440 minutes following insulin stimulation was monitored using microarrays and compared to a control condition. About 1700 genes were selected as differentially expressed based on their treated minus control profile, thus allowing the detection of even small but systematic changes in gene expression. Genes were clustered in 7 groups according to their time expression profile and classified into 15 functional categories that can support the biological effects of insulin, based on Gene Ontology enrichment analysis. In terms of endothelial function, the most prominent processes affected were NADH dehydrogenase activity, N-terminal myristoylation domain binding, nitric-oxide synthase regulator activity and growth factor binding. Pathway-based enrichment analysis revealed “Electron Transport Chain” significantly enriched.Results were validated on genes belonging to “Electron Transport Chain” pathway, using quantitative RT-PCR.ConclusionsAs far as we know, this is the first systematic study in the literature monitoring transcriptional response to insulin in endothelial cells, in a time series microarray experiment. Since chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation, some of the genes identified in the present work are potential novel candidates in diabetes complications related to endothelial dysfunction.

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Phosphatidylinositol 3-Kinase

Cited by 34 publications

References 29 publications

Platelet-derived Growth Factor-BB-mediated Activation of Akt Suppresses Smooth Muscle-specific Gene Expression through Inhibition of Mitogen-activated Protein Kinase and Redistribution of Serum Response Factor

Platelet-derived Growth Factor-BB-mediated Activation of Akt Suppresses Smooth Muscle-specific Gene Expression through Inhibition of Mitogen-activated Protein Kinase and Redistribution of Serum Response Factor

Cyclocarya paliurus (Batal.) Ijinskaja Aqueous Extract (CPAE) Ameliorates Obesity by Improving Insulin Signaling in the Hypothalamus of a Metabolic Syndrome Rat Model

The Transcriptional Response in Human Umbilical Vein Endothelial Cells Exposed to Insulin: A Dynamic Gene Expression Approach

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