Activation of AMP kinase α1 subunit induces aortic vasorelaxation in mice

Goirand, Françoise; Solar, Myriam; Athéa, Yoni; Viollet, Benoı̂t; Matéo, Philippe; Fortin, D.; Leclerc, Jocelyne; Hoerter, Jacqueline; Ventura‐Clapier, Renée; Garnier, Anne

doi:10.1113/jphysiol.2007.132589

Cited by 106 publications

(127 citation statements)

References 23 publications

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“…In addition, it was recently shown that smooth muscle ␣1-AMPK subunit activation induces vasorelaxation of mouse aorta independent of NO and the presence of endothelium (40), again in line with our findings. Unlike cardiac or skeletal muscles, vascular smooth muscle can maintain tonic force with low ATP turnover in the continued presence of vasoconstrictor.…”

Section: Discussionsupporting

confidence: 81%

AMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase

Horman

Morel²,

Vertommen

et al. 2008

Journal of Biological Chemistry

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108

131

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Smooth muscle contraction is initiated by a rise in intracellu-The activity of smMLCK itself can be modulated by phosphorylation, which changes its V max or affinity for Ca 2ϩ /CaM. smMLCK is phosphorylated at two sites (7, 8) by cAMP-dependent protein kinase (PKA). One site (site A, corresponding to Ser 815 in chicken and Ser 992 in rabbit smMLCK and conserved in the human, mouse, and rat sequences) lies in the C-terminal CaM-binding domain. Treatment with PKA inactivates MLCK by decreasing its affinity for Ca 2ϩ /CaM (9). Similar changes in affinity have also been observed after phosphorylation by Ca 2ϩ /CaM-dependent kinase II (7) and protein kinase C (10). Moreover, smMLCK contains several consensus sequences for proline-directed kinases, and phosphorylation by MAPK increases the V max with no change in affinity for Ca 2ϩ / CaM (10, 11).

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Section: Discussionsupporting

confidence: 81%

AMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase

Horman

Morel²,

Vertommen

et al. 2008

Journal of Biological Chemistry

Self Cite

108

131

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“…AMPK activity can be regulated by a low energy state (increases in the AMP/ATP ratio), phosphorylation of Thr 172 and Ser 485/491 of the α subunit, and stresses such as reactive oxygen species (ROS), hypoxia, and genotoxic drugs (Stein et al, 2000;Hawley et al, 2003;Hurley et al, 2006). AMPK has various cellular functions, including the regulation of cellular metabolism, ion channels, and gene expression (Hardie, 2004), activation of glucose transport during hypoxia and ischemia via eNOS phosphorylation (Li et al, 2004), cell cycle arrest via p53 phosphorylation (Jones et al, 2005), differentiation of endothelial progenitor cells via eNOS activation (Li et al, 2008), inhibition of protein synthesis via TSC1/2, induction of aortic vasorelaxation in mice (Goirand et al, 2007), and regulation of apoptotic cell death signals (Cao et al, 2008;Kim et al, 2008;Lee et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts

et al. 2010

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In addition to its well-known glycolytic activity, GAPDH displays multiple functions, such as nuclear RNA export, DNA replication and repair, and apoptotic cell death. This functional diversity depends on its intracellular localization. In this study, we explored the signal transduction pathways involved in the nuclear translocation of GAPDH using confocal laser scanning microscopy of immunostained human diploid fibroblasts (HDFs). GAPDH was present mainly in the cytoplasm when cultured with 10% FBS. Serum depletion by culturing cells in a serum-free medium (SFM) led to a gradual accumulation of GAPDH in the nucleus, and this nuclear accumulation was reversed by the re-addition of serum or growth factors, such as PDGF and lysophosphatidic acid. The nuclear export induced by the re-addition of serum or growth factors was prevented by LY 294002 and SH-5, inhibitors of phosphoinositide 3-kinase (PI3K) and Akt/protein kinase B, respectively, suggesting an involvement of the PI3K signaling pathway in the nuclear export of GAPDH. In addition, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulated the nuclear translocation of GAPDH and prevented serum-and growth factor-induced GAPDH export. AMPK inhibition by compound C or AMPK depletion by siRNA treatment partially prevented SFM-and AICAR-induced nuclear translocation of GAPDH. Our data suggest that the nuclear translocation of GAPDH might be regulated by the PI3K signaling pathway acting mainly as a nuclear export signal and the AMPK signaling pathway acting as a nuclear import signal.

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“…21 AMPK activation causes the NO-mediated relaxation in the spontaneously hypertensive rats. [25][26][27][28] AMPK, at the same time, causes the endothelium independent vascular smooth muscle relaxation in the aort preparations of the Mouse. 27 …”

Section: Adenosine Monophosphate-activated Protein Kinase Pathwaymentioning

confidence: 99%

“…It therefore shows a vasoprotective effect. [25][26][27] It is thought that the vasoprotective effects of the therapeutic agents like, metformin 24 , thiazolidinediones and statins also occur via the AMPK activation. 21 AMPK activation causes the NO-mediated relaxation in the spontaneously hypertensive rats.…”

Section: Adenosine Monophosphate-activated Protein Kinase Pathwaymentioning

confidence: 99%

“…On the other hand, it causes endothelium independent relaxation by decreasing intracellular Ca +2 sensitivity and vascular tonus through activating MLCK in vascular smooth muscle cell. [25][26][27] In summary, ROCK activation makes hypertension and diabetes like pathologies more critical by causing increase in vascular contraction. Increase in the AMPK activation, can help fixing vascular complications caused by these pathologies with its vasculoprotective effect.…”

Section: Rho-kinase and Adenosine Monophosphate-activated Protein Kinmentioning

confidence: 99%

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Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Balcilar

Özakça

Altan

2017

tjps

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Vascular tonus is controlled by endothelium-derived relaxing factor (EDRF), endothelium-derived hyperpolarizing factor (EDHF) and endotheliumderived contracting factor (EDCF) under physiological circumstances. In pathological conditions, impairment of endothelium-derived relaxation can be caused by both decrease in EDRF release and increase in EDCF release. The increase in EDCF is observed with diseases such as hypertension and diabetes. The contribution of Rho-kinase and activated protein kinase (AMPK), which have opposite effects, to the increased EDCF responses was investigated. Rho-kinases are the effectors of Rho which is one of the small guanosine triphosphate-binding proteins. They increase cytosolic Ca +2 concentration and cause vascular smooth muscle to contract, keeping myosin light chain (MLC) in phosphorylated state by affecting myosin phosphatase target subunit which dephosphorylates the MLC. The activities of Rho-kinases increase with the increase of EDCF function. AMPK is the energy sensor of the cell. It provides a vasculoprotective effect by causing endothelium-dependent and endothelium-independent relaxation in smooth muscle. In contrast to Rho-kinase pathway activity, AMPK pathway activity decreases with diseases in which the EDCF function increases. In cases such as diabetes and hypertension that endothelial function impairs toward vasocontraction, it is considered that evaluating Rho-kinase and AMPK pathways which mediate contraction and relaxation in vascular smooth muscle respectively, would provide clues on choosing therapeutic target for pathologies in which endothelial dysfunction is observed. ÖZFizyolojik koşullarda vasküler tonus endotel kaynaklı rahatlatıcı faktörü (EDRF), endotel kaynaklı hiperpolarizasyon faktörü (EDHF) ve endotel kaynaklı kasılma faktörü (EDCF) tarafından kontrol edilmektedir. Patolojik durumlarda endotel kaynaklı gevşemenin azalması, EDRF üretimindeki azalmaya bağlı olabileceği gibi EDCF düzeyinin artmasına da bağlı olabilmektedir. EDCF hipertansiyon, diyabet gibi hastalıklarda artmaktadır. Diyabet, hipertansiyon gibi patolojik koşullarda artan EDCF yanıtına birbirine ters etki yapan Rho-kinaz ve aktive protein kinaz (AMPK) yolaklarının katkısı olabileceği düşünülmektedir. Rho-kinazlar küçük guanozin trifosfat-bağlı proteinlerden biri olan Rho'nun efektörüdür. Rho-kinazlar hafif zincir miyozini (MLC) defosforile eden miyozin fosfataz hedef altbirimine etki ederek MLC'nin fosforile halde kalmasının sağlayarak sitozolik Ca +2 konsantrasyonu artırır ve vasküler düz kasın kasılmasına neden olurlar. Rho-kinazların aktivitesi EDCF yanıtlarının arttığı hipertansiyon, kalp yetmezliği ve diyabet gibi hastalıklarda artmaktadır. AMPK ise hücrenin enerji sensörü olarak düşünülmektedir. Vasküler düz kasta endotel bağımlı ve bağımsız gevşemeyi sağlayarak vasküloprotektif etki sağlamaktadır. AMPK'nin aktivitesi Rho-kinaz yolağının aktivitesinin tersine EDCF fonksiyonunun arttığı hipertansiyon ve diyabet gibi hastalıklarda azalmaktadır. Endotel fonksiyonunun vazokonstriksiyon y...

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Activation of AMP kinase α1 subunit induces aortic vasorelaxation in mice

Cited by 106 publications

References 23 publications

AMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase

AMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase

Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

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