AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells

Miranda, Lisa; Carpentier, Sarah; Płatek, Anna E.; Hussain, Nusrat; Gueuning, Marie-Agnès; Vertommen, Didier; Ozkan, Yurda; Sid, Brice; Hue, Louis; Courtoy, Pierre J.; Rider, Mark H.; Horman, Sandrine

doi:10.1016/j.bbrc.2010.04.151

Cited by 65 publications

(66 citation statements)

References 41 publications

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“…Inhibition of laminar AMPK activation (such as seen here in response to high‐CHO feeding) also may alter the differentiation phenotype and adherence of LBEC, as has been shown in other systems 35, 36, 39. Decreased AMPK activation has been reported to result in activation of mTORC1/p70S6K/RPS6 signaling (known to be important in the poorly differentiated, less adhesive phenotype of tumor cells) 49, 50.…”

Section: Discussionsupporting

confidence: 57%

“…In addition to its well‐characterized roles in energy regulation, AMPK more recently has been shown to be important in the maintenance and dynamic repair of intercellular tight junctions,35, 36 enhancement of cell‐cell contacts,37 induction of phenotypic differentiation, and determination of cell polarity 38, 39, 40. Although the net effects of AMPK activation or inhibition on the function of the equine LBEC are unknown, it may play a role in this highly polarized, structurally critical cell type.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5′‐Adenosine Monophosphate‐Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies

Burns

Watts

Weber

et al. 2014

Veterinary Internal Medicne

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BackgroundIn EMS‐associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5′‐Adenosine‐monophosphate‐activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR.Hypothesis/ObjectivesTo characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge.AnimalsTwenty‐two mixed‐breed ponies.MethodsImmunohistochemistry and immunoblotting for total AMPK and phospho(P)‐AMPK and RT‐qPCR for AMPK‐responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7‐day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low‐CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high‐CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean).Results5′‐Adenosine‐monophosphate‐activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high‐CHO diet resulted in significantly decreased laminar [P‐AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P‐AMPK]. An inverse correlation existed between [blood glucose] and laminar [P‐AMPK] in obese ponies on a high‐CHO diet.Conclusions and Clinical ImportanceLaminar tissue exhibited a normal response to a high‐CHO diet (decreased [P‐AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5′‐Adenosine Monophosphate‐Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies

Burns

Watts

Weber

et al. 2014

Veterinary Internal Medicne

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“…However, AMPK stimulates human umbilical vein endothelium cell migration (46) and induces transendothelial lymphocyte migration by endothelial nitric-oxide synthase activation (47). In addition, hypertonicity-and A769662-induced AMPK activation triggers actin cytoskeleton remodeling via phosphorylation of ROCK downstream targets in MadinDarby Canine Kidney cells (48). Therefore, the role of AMPK in cell migration may be dependent on which extracellular factors are stimulated or occur in a cell type-specific manner.…”

Section: Discussionmentioning

confidence: 99%

Activation of AMP-activated Protein Kinase Is Essential for Lysophosphatidic Acid-induced Cell Migration in Ovarian Cancer Cells

Kim

Park

Lim

et al. 2011

Journal of Biological Chemistry

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Lysophosphatidic acid (LPA) is a bioactive phospholipid that affects various biological functions, such as cell proliferation, migration, and survival, through LPA receptors. Among them, the motility of cancer cells is an especially important activity for invasion and metastasis. Recently, AMP-activated protein kinase (AMPK), an energy-sensing kinase, was shown to regulate cell migration. However, the specific role of AMPK in cancer cell migration is unknown. The present study investigated whether LPA could induce AMPK activation and whether this process was associated with cell migration in ovarian cancer cells. We found that LPA led to a striking increase in AMPK phosphorylation in pathways involving the phospholipase C-␤3 (PLC-␤3) and calcium/calmodulin-dependent protein kinase kinase ␤ (CaMKK␤) in SKOV3 ovarian cancer cells. siRNA-mediated knockdown of AMPK␣1, PLC-␤3, or (CaMKK␤) impaired the stimulatory effects of LPA on cell migration. Furthermore, we found that knockdown of AMPK␣1 abrogated LPA-induced activation of the small GTPase RhoA and ezrin/radixin/moesin proteins regulating membrane dynamics as membrane-cytoskeleton linkers. In ovarian cancer xenograft models, knockdown of AMPK significantly decreased peritoneal dissemination and lung metastasis. Taken together, our results suggest that activation of AMPK by LPA induces cell migration through the signaling pathway to cytoskeletal dynamics and increases tumor metastasis in ovarian cancer. Lysophosphatidic acid (LPA)2 has been shown to participate in diverse biological actions, including changes in cell shape, motility, and proliferation, in a variety of cell types (1). Previous studies have shown that LPA has a role in early signaling events, such as Ca 2ϩ mobilization, changes in cAMP accumulation, and the activation of several protein kinases (1-4). Among these pathological processes, the role of LPA in ovarian cancer has been most extensively studied. LPA contributes to the development, progression, and metastasis of ovarian cancer, and its concentration is increased up to 80 M (in comparison to the basal 1-5 M concentration) in both plasma and ascites of ovarian cancer patients (5). In vitro studies have shown that production of LPA levels was constitutively increased in ovarian cancer cells but not in normal ovarian epithelial cells (6, 7). Moreover, in a study of the expression of LPA receptor mRNA and protein levels in ovarian cancer tissues, LPA 2 and LPA 3 were aberrantly up-regulated, but LPA 1 was not changed (8, 9). Overexpression of LPA 2 and LPA 3 are closely associated with tumor progression in ovarian cancer cells (10 -13). As evidence of intracellular signaling in cancer cell migration, LPA induces activation of Ras-MEKK1 (14), Rac1 (15), Ca 2ϩ -dependent Pyk2 (16), and the Rho/ROCK pathway (17), which indicates that dynamic cytoskeletal rearrangement in LPA-mediated cell migration is regulated through the coordination of complex contexts (such as small GTPases, focal adhesion, and Ca 2ϩ -dependent signaling). However, the exact re...

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“…5,22). Knowing that these actors are also regulated by AMPK (20,24,30), it is tempting to postulate a possible action of one or several of these partners in the effect of AMPK activators in the insulin-mediated stimulation of glucose uptake. For instance, the fact that the insulininduced actin cytoskeleton rearrangement is impaired in insulin-resistant conditions (18) reenforces such hypothesis.…”

Section: H475 Study Of the Insulin-sensitizing Effect Of Ampkmentioning

confidence: 99%

Inhibition of the mTOR/p70S6K pathway is not involved in the insulin-sensitizing effect of AMPK on cardiac glucose uptake

Ginion

Auquier

Benton

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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The AMP-activated protein kinase (AMPK) is known to increase cardiac insulin sensitivity on glucose uptake. AMPK also inhibits the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase (p70S6K) pathway. Once activated by insulin, mTOR/p70S6K phosphorylates insulin receptor substrate-1 (IRS-1) on serine residues, resulting in its inhibition and reduction of insulin signaling. AMPK was postulated to act on insulin by inhibiting this mTOR/p70S6K-mediated negative feedback loop. We tested this hypothesis in cardiomyocytes. The stimulation of glucose uptake by AMPK activators and insulin correlated with AMPK and protein kinase B (PKB/Akt) activation, respectively. Both treatments induced the phosphorylation of Akt substrate 160 (AS160) known to control glucose uptake. Together, insulin and AMPK activators acted synergistically to induce PKB/Akt overactivation, AS160 overphosphorylation, and glucose uptake overstimulation. This correlated with p70S6K inhibition and with a decrease in serine phosphorylation of IRS-1, indicating the inhibition of the negative feedback loop. We used the mTOR inhibitor rapamycin to confirm these results. Mimicking AMPK activators in the presence of insulin, rapamycin inhibited p70S6K and reduced IRS-1 phosphorylation on serine, resulting in the overphosphorylation of PKB/Akt and AS160. However, rapamycin did not enhance the insulin-induced stimulation of glucose uptake. In conclusion, although the insulin-sensitizing effect of AMPK on PKB/Akt is explained by the inhibition of the insulin-induced negative feedback loop, its effect on glucose uptake is independent of this mechanism. This disconnection revealed that the PKB/Akt/AS160 pathway does not seem to be the rate-limiting step in the control of glucose uptake under insulin treatment.adenosine 5=-monophosphate-activated protein kinase; protein kinase B/Akt; p70 ribosomal S6 kinase; insulin resistance; metformin A COMMON FEATURE OF TYPE 2 diabetes is insulin resistance of peripheral tissues like cardiac muscle. Insulin resistance is a major risk factor for the development of hypertension, cardiac hypertrophy, and heart failure. In addition, this resistance impairs metabolic effects of insulin such as glucose uptake, which is associated, after an ischemic episode, with a poor recovery of cardiac function during reperfusion (see Refs. 7, 8 for reviews). Knowing that ischemic heart disease is responsible for ϳ50% of the deaths in the diabetic population, the treatment of insulin resistance and the increase of glucose uptake in the diabetic heart remains an important issue. The decrease of the insulin-stimulated glucose uptake in insulinresistant heart is linked, in part, to the impairment of the translocation of the glucose transporter GLUT4 to the plasma membrane (see Ref. 10 for a review). The defect in GLUT4 translocation is, moreover, associated with an alteration of the insulin-induced activation of the protein kinase B (PKB)/Akt signaling pathway (17,26).In nondiabetic cardiomyocytes, insulin binding to its receptor induces th...

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AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells

Cited by 65 publications

References 41 publications

Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5′‐Adenosine Monophosphate‐Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies

Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5′‐Adenosine Monophosphate‐Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies

Activation of AMP-activated Protein Kinase Is Essential for Lysophosphatidic Acid-induced Cell Migration in Ovarian Cancer Cells

Inhibition of the mTOR/p70S6K pathway is not involved in the insulin-sensitizing effect of AMPK on cardiac glucose uptake

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