Epigallocatechin Gallate, a Green Tea Polyphenol, Mediates NO-dependent Vasodilation Using Signaling Pathways in Vascular Endothelium Requiring Reactive Oxygen Species and Fyn

Kim, Jeong‐A; Formoso, Gloria; Li, Yunhua; Potenza, Maria Assunta; Marasciulo, Flora L.; Montagnani, Monica; Quon, Michael J.

doi:10.1074/jbc.m609725200

Cited by 211 publications

(157 citation statements)

References 62 publications

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“…33) EGCG also stimulates activation of endothelial nitric oxide synthase (eNOS) through activation of PI3K/Akt pathway. 34) These findings suggest that the modification of PI3K activation by flavonoids is different for concentrations, cell types, and classes of stimulants.…”

Section: Discussionmentioning

confidence: 97%

Inhibitory Mechanisms of Flavonoids on Insulin-Stimulated Glucose Uptake in MC3T3-G2/PA6 Adipose Cells

Nomura

Takahashi

Nagata

et al. 2008

Biological & Pharmaceutical Bulletin

109

110

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Insulin plays a key role in the stimulation of glucose uptake in tissues, such as muscle and adipocytes, as well as in the maintenance of glucose homeostasis. Impairment of insulin's ability to stimulate glucose uptake in the tissues is a major factor responsible for insulin resistance associated with type 2 diabetes.1) The primary mechanism of insulinstimulated glucose uptake in muscle and adipocytes is through the translocation of glucose transporter 4 (GLUT4) from intracellular pools to the plasma membrane.2) Insulin signal transduction is initiated by binding to the insulin receptor, followed by activation of the receptor tyrosine kinase (RTK).3,4) The activated RTK induces activation of downstream signaling pathways, such as phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. The translocation of GLUT4 to the plasma membrane was established to be mediated through the PI3K pathway, based on the use of pharmacological inhibitors, and expression of a dominant negative mutant or constitutively active form of PI3K. [5][6][7][8][9] Flavonoids, which are primarily phenylbenzo-g-pyrone (phenylchromone) derivatives, are polyphenolic compounds present in fruits, vegetables, and beverages.10) It has been reported that flavonoids possess a variety of biological activities, including anti-inflammatory, anti-oxidant, anti-bacterial, anti-cardiovascular disease, and anti-cancer activities. 11)These actions were suggested to result from changes in the activity of a number of intracellular enzymes, including tyrosine kinases, protein kinase C, PI3K, and MAPK. [11][12][13][14] The findings suggest that flavonoids may modify insulin-stimulated glucose uptake by modulating insulin RTK and/or PI3K activity in muscle or adipose cells. Indeed, several reports have shown that flavonoids, such as myricetin, quercetin, catechin-gallate, genistein, and naringenin, inhibited insulinstimulated glucose uptake in adipocytes. [15][16][17] However, the inhibitory mechanisms may be different for flavonoids of different classes or structures. Bazuine et al. 15) reported that genistein, an isoflavone, directly inhibited insulin-stimulated glucose uptake in mouse 3T3-L1 adipocytes. On the other hand, naringenin, a flavanone, inhibited insulin-stimulated glucose uptake through blocking PI3K activity in the cell line.17) Therefore, in this study, we investigated the effects of flavonoids on insulin-induced glucose uptake in mouse MC3T3-G2/PA6 adipocytes using a panel of 24 flavonoids, including flavones, flavonols, isoflavones, flavanones, flavanols and flavanonols. MATERIALS AND METHODS MaterialsThe flavones, flavone, apigenin, luteolin and chrysin, the flavonols, kaempferol, quercetin, rutin and morin, the isoflavones, daidzein and genistein, the flavanones, hesperetin, hesperidin and naringenin, the flavanonol, silybin, the flavanols, (ϩ)-catechin and EGCG, fetal bovine serum (FBS) and insulin were purchased from SigmaAldrich Corp. (St. Louis, MO, U.S.A.). The flavone, baicalein, and the flavonols, gal...

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Section: Discussionmentioning

confidence: 97%

Inhibitory Mechanisms of Flavonoids on Insulin-Stimulated Glucose Uptake in MC3T3-G2/PA6 Adipose Cells

Nomura

Takahashi

Nagata

et al. 2008

Biological & Pharmaceutical Bulletin

109

110

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“…12) Phosphorylation of eNOS at Ser-1177 has been found to be associated with increases in enzyme activation and NO production. 15) Furthermore, several studies have reported that polyphenols such as epigallocatechin-3-gallate, 21) delphinidin, 22) resveratrol, 23) and PAs from grape skin extract 24) increased the phosphorylation of eNOS. Evaluation of persimmon leaf PA-stimulated phosphorylation in HUVECs revealed that ex vivo persimmon leaf PAs at the maximal relaxation concentration caused time-dependent phosphorylation not only of eNOS (Ser-1177), but also of its upstream kinase Akt (Ser-473) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive and Vasorelaxant Effects of Water-Soluble Proanthocyanidins from Persimmon Leaf Tea in Spontaneously Hypertensive Rats

Kawakami

Aketa

Sakai

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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“…18) Although these effects of polyphenol treatment could be secondary to its protective effect against oxidant stress, there is preliminary evidence indicating that polyphenols themselves may contribute to regulation of the vascular tone. 19) When administered in vitro, resveratrol (RV) enhances endothelial vasorelaxation by potentiating NO synthase and increasing the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), suggesting that RV alone has a vasodilatory effect. 19) We hypothesized that short-term treatment with polyphenols improves endothelial dysfunction related to diabetes.…”

mentioning

confidence: 99%

“…19) When administered in vitro, resveratrol (RV) enhances endothelial vasorelaxation by potentiating NO synthase and increasing the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), suggesting that RV alone has a vasodilatory effect. 19) We hypothesized that short-term treatment with polyphenols improves endothelial dysfunction related to diabetes.…”

mentioning

confidence: 99%

Effect of Short-term Polyphenol Treatment on Endothelial Dysfunction and Thromboxane A<sub>2</sub> Levels in Streptozotocin-Induced Diabetic Mice

Taguchi

Hida

Matsumoto

et al. 2014

Biological & Pharmaceutical Bulletin

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Diabetes is characterized by the development of endothelial dysfunction, which affects both nitric oxide (NO)-mediated relaxation and endothelium-derived contracting factors, associated with vascular oxidative stress. There is a growing body of evidence suggesting that polyphenols have several beneficial effects, such as antioxidant and anti-inflammatory activities. This study investigated whether short-term treatment with polyphenols (chlorogenic acid (CA), morin (MO), resveratrol (RV)) can improve endothelial dysfunction related to diabetes. Aorta reactivity was determined in organ chambers, and we measured NO production and thromboxane B 2 (TXB 2 ; a metabolite of TXA 2 ) from aortas in response to acetylcholine (ACh). Streptozotocin (

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Epigallocatechin Gallate, a Green Tea Polyphenol, Mediates NO-dependent Vasodilation Using Signaling Pathways in Vascular Endothelium Requiring Reactive Oxygen Species and Fyn

Cited by 211 publications

References 62 publications

Inhibitory Mechanisms of Flavonoids on Insulin-Stimulated Glucose Uptake in MC3T3-G2/PA6 Adipose Cells

Inhibitory Mechanisms of Flavonoids on Insulin-Stimulated Glucose Uptake in MC3T3-G2/PA6 Adipose Cells

Antihypertensive and Vasorelaxant Effects of Water-Soluble Proanthocyanidins from Persimmon Leaf Tea in Spontaneously Hypertensive Rats

Effect of Short-term Polyphenol Treatment on Endothelial Dysfunction and Thromboxane A<sub>2</sub> Levels in Streptozotocin-Induced Diabetic Mice

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