(-)-Epicatechin-induced calcium independent eNOS activation: roles of HSP90 and AKT

Ramírez-Sánchez, Israel; Aguilar, Hugo; Ceballos, Guillermo; Villarreal, Francisco

doi:10.1007/s11010-012-1405-9

Cited by 30 publications

(35 citation statements)

References 30 publications

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“…Mice treated with epicatechin alone (without exercise) have structural and metabolic changes in skeletal and cardiac muscle similar to those of mice undergoing exercise (60). Epicatechin alone and in combination with exercise has an additive effect to stimulate myocardial angiogenesis (70). Obese, diabetic db/db mice have prolonged lifespan, along with a decrease in markers of inflammation and LDL-cholesterol when treated with epicatechin (79).…”

Section: E682mentioning

confidence: 94%

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Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

Munir

Chandrasekaran

Gao

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Munir KM, Chandrasekaran S, Gao F, Quon MJ. Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications. Am J Physiol Endocrinol Metab 305: E679 -E686, 2013. First published July 30, 2013 doi:10.1152/ajpendo.00377.2013.-The rising epidemic of diabetes is a pressing issue in clinical medicine worldwide from both healthcare and economic perspectives. This is fueled by overwhelming increases in the incidence and prevalence of obesity. Obesity and diabetes are characterized by both insulin resistance and endothelial dysfunction that lead to substantial increases in cardiovascular morbidity and mortality. Reciprocal relationships between insulin resistance and endothelial dysfunction tightly link metabolic diseases including obesity and diabetes with their cardiovascular complications. Therefore, therapeutic approaches that target either insulin resistance or endothelial dysfunction alone are likely to simultaneously improve both metabolic and cardiovascular pathophysiology and disease outcomes. Moreover, combination therapies with agents targeting distinct mechanisms are likely to have additive or synergistic benefits. Conventional therapies for diabetes and its cardiovascular complications that are both safe and effective are insufficient to meet rising demand. Large, robust, epidemiologic studies demonstrate beneficial metabolic and cardiovascular health effects for many functional foods containing various polyphenols. However, precise molecular mechanisms of action for food polyphenols are largely unknown. Moreover, translation of these insights into effective clinical therapies has not been fully realized. Nevertheless, some functional foods are likely sources for safe and effective therapies and preventative strategies for metabolic diseases and their cardiovascular complications. In this review, we emphasize recent progress in elucidating molecular, cellular, and physiological actions of polyphenols from green tea (EGCG), cocoa (ECG), and citrus fruits (hesperedin) that are related to improving metabolic and cardiovascular pathophysiology. We also discuss a rigorous comprehensive approach to studying functional foods that is essential for developing novel, effective, and safe medications derived from functional foods that will complement existing conventional drugs. insulin resistance; endothelial dysfunction; functional foods; polyphenols OBESITY, PREDIABETES, METABOLIC SYNDROME, and diabetes are characterized by insulin resistance, endothelial dysfunction and resultant cardiovascular complications (38,39,45).

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Section: E682mentioning

confidence: 94%

“…In human coronary artery endothelial cells, epicatechin phosphorylates and activates eNOS through Akt and a complex with HSP90 (70). Incubating human umbilical vein endothelial cells with cocoa extract inhibits angiotensinconverting enzyme activity and enhances NO production (64).…”

Section: E682mentioning

confidence: 99%

Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

Munir

Chandrasekaran

Gao

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Many studies have reported the interaction of HSP90 and eNOS in various disease prevention (Ramirez-Sanchez et al, 2012;Vladic et al, 2011;Simet et al, 2013). It was reported that Hsp90 inhibitor was able to inhibit the eNOS and Hsp90 interaction and decrease the level of eNOS (Prangsaengtong et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved

He¹,

Song²,

Li³

2015

Brain Research

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“…Of interest is the observation that under Ca 2+ -free conditions, EPI is uniquely capable of inducing NO production secondary to eNOS phosphorylation via AKT activation independently of the translocation of the enzyme from the plasmalemma. 6-6 However, no studies have examined the differential effects of EPI restricting its presence to the plasmalemma.…”

mentioning

confidence: 99%

Cell membrane mediated (−)-epicatechin effects on upstream endothelial cell signaling: Evidence for a surface receptor

Moreno‐Ulloa¹,

Romero-Perez²,

Villarreal³

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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The consumption of cacao-derived products, particularly in the form of dark chocolate is known to provide beneficial cardiovascular effects in normal individuals and in those with vascular dysfunction (reduced nitric oxide [NO] bioavailability and/or synthesis). Upstream mechanisms by which flavonoids exert these effects are poorly understood and may involve the participation of cell membrane receptors. We previously demonstrated that the flavanol (-)-epicatechin (EPI) stimulates NO production via Ca+2-independent eNOS activation/phosphorylation. We wished to investigate the plausible participation of a cell surface receptor using a novel cell-membrane impermeable EPI-Dextran conjugate (EPI-Dx). Under Ca2+-free conditions, human coronary artery endothelial cells (HCAEC) were treated for 10 min with EPI or EPI-Dx at equimolar concentrations (100 nM). Results demonstrate that both EPI and EPI-Dx induced the phosphorylation/activation of PI3K, PDK-1, AKT and eNOS. Interestingly, EPI-Dx effects were significantly higher in magnitude than those of EPI alone. The capacity of EPI-Dx to stimulate cell responses supports the existence of an EPI cell membrane receptor mediating eNOS activation.

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(-)-Epicatechin-induced calcium independent eNOS activation: roles of HSP90 and AKT

Cited by 30 publications

References 30 publications

Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved

Cell membrane mediated (−)-epicatechin effects on upstream endothelial cell signaling: Evidence for a surface receptor

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