AMP-Activated Protein Kinase Inhibits Angiotensin II–Stimulated Vascular Smooth Muscle Cell Proliferation

Nagata, Daisuke; Takeda, Ryo; Sata, Masataka; Saito, Hiroshi; Suzuki, Emiko; Nagano, Tetsuo; Hirata, Yasunobu

doi:10.1161/01.cir.0000136025.96811.76

Cited by 188 publications

(169 citation statements)

References 42 publications

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“…Recently, it has been discovered that AMPK inhibits Ang II-stimulated vascular smooth muscle cell proliferation. 20 Several reports indicate that the antidiabetic adipocytokine adiponectin, which activates AMPK, has antiatherosclerotic effects. [21][22][23] Moreover, adiponectin activates AMPK and inhibits agonist-stimulated myocardial hypertrophy and ERK activation, as well as ERK transduction.…”

Section: Discussionmentioning

confidence: 99%

Activation of AMP-Activated Protein Kinase Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts

et al. 2006

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Abstract-AMP-activated kinase (AMPK) is a highly conserved heterotrimeric kinase that functions as a metabolic regulator of cellular enzymes involved in carbohydrate and fat metabolism, which regulate ATP conservation and synthesis. Here, we investigated whether AMPK signaling has a role in the regulation of angiotensin II (Ang II)-induced proliferation in rat cardiac fibroblasts. Aminoimidazole-4-carboxamide-1-␤-ribofuranoside (AICAR) activated AMPK in rat cardiac fibroblasts and increased Ang II-induced extracellular signal-regulated kinase 1/2 phosphorylation and activity. AICAR also increased Ang II-induced c-fos mRNA expression in the cells. Key Words: cardiac function Ⅲ angiotensin Ⅲ hypertrophy Ⅲ signal transduction A MP-activated kinase (AMPK) is a highly conserved heterotrimeric kinase that functions as a metabolic regulator of cellular enzymes involved in carbohydrate and fat metabolism, which regulate ATP conservation and synthesis. 1 AMPK is activated by conditions that increase the AMP:ATP ratio, such as exercise and metabolic stress. AMPK has been most extensively examined under conditions of stress, such as exercise and hypoxia-ischemia. When the AMP:ATP ratio increases, AMPK is activated by AMPK kinase to combine with AMP, thus inducing a conformational change and decreasing the AMP:ATP ratio by switching off ATP-consuming pathways and switching on ATP-generating pathways. 1 Considerable information exists regarding the regulation of AMPK activation in a variety of cell types, including cardiac cells. 2,3 There is a correlation between AMPK activation and the development of cardiac hypertrophy. 4,5 Pressure overload-induced hypertrophic cardiomyopathy is associated with increased AMPK activity. 4 In addition, AMPK plays a role in familial Wolff-Parkinson-White syndrome and hypertrophic cardiomyopathy via mutations in PRKAG2, a gene encoding the ␥2 subunit of AMPK. 6 -8 On the other hand, recent evidence indicates that AMPK activation inhibits proteins synthesis 9,10 and might, thus, be expected to reduce the development of hypertrophy. Although much has been learned about the role of AMPK in the development of cardiac hypertrophy, the molecular mechanism by which AMPK regulates cardiac hypertrophy is still unclear.Interstitial fibroblast proliferation and collagen accumulation is associated with compensatory remodeling of the hypertrophic myocardium, 11,12 and structural remodeling leads to diastolic and systolic dysfunction. 13 Angiotensin (Ang) II is closely involved in cardiac remodeling by stimulating hyperplastic growth of cardiac fibroblasts 14 and the synthesis of extracellular matrix proteins. 12 Therefore, we investigated the role of AMPK in cardiac remodeling using cardiac fibroblasts. We used 5-aminoimidazole-4-carboxamide-1-␤-ribofuranoside (AICAR), which is an adenosine analog, as well as cell-permeable activator of AMPK and a small interfering RNA (siRNA) for AMPK, which is an AMPK inhibitor. We examined the effects of both the AMPK activator and inhibitor on the extracellular sign...

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Section: Discussionmentioning

confidence: 99%

Activation of AMP-Activated Protein Kinase Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts

et al. 2006

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“…Additionally, AMPK activation not only inhibits cancer cell growth but also non-cancer cells, such as vascular smooth muscle cells, endothelial cells, etc (Zhang et al, 2008;Song et al, 2011). Subcutaneous injection of AICAR, which is an AMPK activator, for 2 weeks suppresses neointimal formation after transluminal mechanical injury of the rat femoral artery (Nagata et al, 2004). In deed, resveratrol has been reported to stimulate AMPK in kidney collecting duct cells and neurons (Dasgupta et al, 2007;Weixel et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Inhibits Oesophageal Adenocarcinoma Cell Proliferation via AMP-activated Protein Kinase Signaling

Guanghua

Wang²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Resveratrol has been examined in several model systems for potential effects against cancer. Adenosine monophosphate-activated protein kinase (AMPK) is reported to suppress proliferation in most eukaryocyte cells. Whether resveratrol via AMPK inhibits proliferation of oesophageal adenocarcinoma cells (OAC) is unknown. The aim of this study was to determine the roles of AMPK in the protective effects of resveratrol in OAC proliferation and to elucidate the underlying mechanisms. Treatment of cultured OAC derived from human subjects or cell lines with resveratrol resulted in decreased cell proliferation. Further, inhibition of AMPK by pharmacological reagent or genetical approach abolished resveratrol-suppressed OAC proliferation, reduced the level of p27 Kip1 , a cyclin-dependent kinase inhibitor, and increased the levels of S-phase kinase-associated protein 2 (Skp2) of p27 Kip1 -E3 ubiquitin ligase and 26S proteasome activity reduced by resveratrol. Furthermore, gene silencing of p27 Kip1 reversed resveratrol-suppressed OAC proliferation. In conclusion, these findings indicate that resveratrol inhibits Skp2-mediated ubiquitylation and 26S proteasome-dependent degradation of p27 Kip1 via AMPK activation to suppress OAC proliferation.

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“…AMP-activated protein kinase (AMPK) regulates the involved cellular processes in cellular energy status (Hardie and Carling 1997). Recently, scientifi c evidences have shown that AMPK activation may inhibit the cell proliferation and induce cell apoptosis in cancer cells (Nagata et al 2004). It has been suggested that curcumin-induced cell death in CaOV3 ovarian cancer cells through activating p38-dependent AMPK is reversible by AMPK and p38 inhibitors (Pan et al 2008).…”

Section: Th E Eff Ect Of C Longa and Curcumin On The Female Reproducmentioning

confidence: 99%

The effects of Curcuma longa and curcumin on reproductive systems

Mohebbati

Anaeigoudari

Khazdair

2017

Endocrine Regulations

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Objective. Curcuma longa (C. longa) was used in some countries such as China and India for various medicinal purposes. Curcumin, the active component of C. longa, is commonly used as a coloring agent in foods, drugs, and cosmetics. C. longa and curcumin have been known to act as antioxidant, anti-infl ammatory, anti-mutagen, and anti-carcinogenic agents. Th e attempt of the present review was to give an eff ort on a detailed literature survey concentrated on the protective eff ects of C. longa and curcumin on the reproductive organs activity.Methods. Th e databases such as, PubMed, Web of Science, Google Scholar, Scopus, and IranMedex, were considered. Th e search terms were "testis" or "ovary" and "Curcuma longa", "curcumin", "antioxidant eff ect", "anti-infl ammatory eff ect" and "anti-cancer eff ect".Results. C. longa and curcumin inhibited the production of the tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) and increased the caspases (3, 8 and 9) activities in HL-60 prostate cancer. Furthermore, C. longa and curcumin suppressed the vascular endothelial growth factor (VEGF), phosphorylated signal transducers and activators of the transcription 3 (STAT) and matrix metalloproteinase-9 (MMP-9) in ovarian cancer cell line.Conclusion. C. longa and curcumin might decrease the risk of cancer and other malignant diseases in the reproductive system. C. longa and curcumin have a protective eff ect on the reproductive organs activity such as, anti-infl ammatory, anti-apoptotic, and antioxidant eff ects in normal cells but showed pro-apoptotic eff ects in the malignant cells. Th erefore, diff erent eff ects of C. longa and curcumin are dependent on the doses and the type of cells used in various models studied.

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AMP-Activated Protein Kinase Inhibits Angiotensin II–Stimulated Vascular Smooth Muscle Cell Proliferation

Cited by 188 publications

References 42 publications

Activation of AMP-Activated Protein Kinase Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts

Activation of AMP-Activated Protein Kinase Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts

Resveratrol Inhibits Oesophageal Adenocarcinoma Cell Proliferation via AMP-activated Protein Kinase Signaling

The effects of Curcuma longa and curcumin on reproductive systems

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