scholarly journals Regulation of the creatine transporter by AMP-activated protein kinase in kidney epithelial cells

2010 ◽  
Vol 299 (1) ◽  
pp. F167-F177 ◽  
Author(s):  
Hui Li ◽  
Ramon F. Thali ◽  
Christy Smolak ◽  
Fan Gong ◽  
Rodrigo Alzamora ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Proximal Tubule ◽  
Apical Membrane ◽  
High Energy ◽  
Whole Body ◽  
Creatine Transporter ◽  
Creatine Uptake ◽  
Kidney Epithelial Cells ◽  
Amp Activated Protein Kinase

The metabolic sensor AMP-activated protein kinase (AMPK) regulates several transport proteins, potentially coupling transport activity to cellular stress and energy levels. The creatine transporter (CRT; SLC6A8) mediates creatine uptake into several cell types, including kidney epithelial cells, where it has been proposed that CRT is important for reclamation of filtered creatine, a process critical for total body creatine homeostasis. Creatine and phosphocreatine provide an intracellular, high-energy phosphate-buffering system essential for maintaining ATP supply in tissues with high energy demands. To test our hypothesis that CRT is regulated by AMPK in the kidney, we examined CRT and AMPK distribution in the kidney and the regulation of CRT by AMPK in cells. By immunofluorescence staining, we detected CRT at the apical pole in a polarized mouse S3 proximal tubule cell line and in native rat kidney proximal tubules, a distribution overlapping with AMPK. Two-electrode voltage-clamp (TEV) measurements of Na+-dependent creatine uptake into CRT-expressing Xenopus laevis oocytes demonstrated that AMPK inhibited CRT via a reduction in its Michaelis-Menten Vmax parameter. [14C]creatine uptake and apical surface biotinylation measurements in polarized S3 cells demonstrated parallel reductions in creatine influx and CRT apical membrane expression after AMPK activation with the AMP-mimetic compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside. In oocyte TEV experiments, rapamycin and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-monophosphate (ZMP) inhibited CRT currents, but there was no additive inhibition of CRT by ZMP, suggesting that AMPK may inhibit CRT indirectly via the mammalian target of rapamycin pathway. We conclude that AMPK inhibits apical membrane CRT expression in kidney proximal tubule cells, which could be important in reducing cellular energy expenditure and unnecessary creatine reabsorption under conditions of local and whole body metabolic stress.

scholarly journals Regulation of Megalin membrane traffic by AMP‐activated protein kinase in kidney proximal tubule epithelial cells

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Nikol Leshchyshyn ◽  
Laura Orofiamma ◽  
Christian Delos Santos ◽  
Sadia Rahmani ◽  
Costin Antonescu
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Proximal Tubule ◽  
Membrane Traffic ◽  
Kidney Proximal Tubule ◽  
Amp Activated Protein Kinase

scholarly journals Regulation of proximal tubule vacuolar H+-ATPase by PKA and AMP-activated protein kinase

2014 ◽  
Vol 306 (9) ◽  
pp. F981-F995 ◽  
Author(s):  
Mohammad M. Al-bataineh ◽  
Fan Gong ◽  
Allison L. Marciszyn ◽  
Michael M. Myerburg ◽  
Núria M. Pastor-Soler
Keyword(s):  
Protein Kinase ◽  
Proximal Tubule ◽  
Apical Membrane ◽  
Collecting Duct ◽  
Phosphodiesterase Inhibitor ◽  
Cell Monolayers ◽  
Apical Pole ◽  
Kidney Slices ◽  
Immunofluorescence Labeling ◽  
Amp Activated Protein Kinase

The vacuolar H+-ATPase (V-ATPase) mediates ATP-driven H+ transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress.

Exercise and MEF2–HDAC interactions

2007 ◽  
Vol 32 (5) ◽  
pp. 852-856 ◽  
Author(s):  
Sean L. McGee
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Nuclear Export ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Positive Health ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase ◽  
Body Energy ◽  
Skeletal Muscle Adaptations

Exercise increases the metabolic capacity of skeletal muscle, which improves whole-body energy homeostasis and contributes to the positive health benefits of exercise. This is, in part, mediated by increases in the expression of a number of metabolic enzymes, regulated largely at the level of transcription. At a molecular level, many of these genes are regulated by the class II histone deacetylase (HDAC) family of transcriptional repressors, in particular HDAC5, through their interaction with myocyte enhancer factor 2 transcription factors. HDAC5 kinases, including 5′-AMP-activated protein kinase and protein kinase D, appear to regulate skeletal muscle metabolic gene transcription by inactivating HDAC5 and inducing HDAC5 nuclear export. These mechanisms appear to participate in exercise-induced gene expression and could be important for skeletal muscle adaptations to exercise.

scholarly journals Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonally defined medium.

1982 ◽  
Vol 95 (1) ◽  
pp. 118-126 ◽  
Author(s):  
S D Chung ◽  
N Alavi ◽  
D Livingston ◽  
S Hiller ◽  
M Taub
Keyword(s):  
Epithelial Cells ◽  
Proximal Tubule ◽  
Primary Cultures ◽  
Sugar Transport ◽  
Optimal Growth ◽  
Proximal Tubules ◽  
Rabbit Kidney ◽  
Metabolic Inhibitor ◽  
Gamma Glutamyl Transpeptidase ◽  
Kidney Epithelial Cells

Primary cultures of rabbit-kidney epithelial cells derived from purified proximal tubules were maintained without fibroblast overgrowth in a hormone-supplemented serum-free medium (Medium RK-1). A hormone-deletion study indicated that the primary cultures derived from purified rabbit proximal tubules required all of the three supplements in Medium RK-1 (insulin, transferrin, and hydrocortisone) for optimal growth but did not grow in response to EGF and T3. In contrast, the epithelial cells in primary cultures derived from an unpurified preparation of rabbit kidney tubules and glomeruli grew in response to EGF and T3, as well as insulin, transferrin, and hydrocortisone. These observations suggest that kidney epithelial cells derived from different segments of the nephron grow differently in response to hormones and growth factors. Differentiated functions of the primary cultures derived from proximal tubules were examined. Multicellular domes were observed, indicative of transepithelial solute transport by the monolayers. The proximal tubule cultures also accumulated alpha-methylglucoside (alpha-MG) against a concentration gradient. However, little or no alpha-MG accumulation was observed in the absence of Na+. Metabolic inhibitor studies also indicated that alpha-MG uptake by the primaries is an energy-dependent process, and depends upon the activity of the Na+/K+ ATPase. Phlorizin at 0.1 mM significantly inhibited 1 mM alpha-MG uptake whereas 0.1 mM phloretin did not have a significant inhibitory effect. Similar observations have been made concerning the Na+-dependent sugar-transport system located on the lumenal side of the proximal tubule, whereas the Na+-independent sugar transporter on the peritubular side is more sensitive to inhibition by phloretin than phlorizin. The cultures also exhibited PTH-sensitive cyclic AMP synthesis and brush-border enzymes typical of proximal cells. However, the activities of the enzymes leucine aminopeptidase, alkaline phosphatase, and gamma-glutamyl-transpeptidase were lower in the cultures than in purified proximal-tubule preparations from which they are derived.

PIKfyve: a new fish in the growing pool of AMPK substrates

2013 ◽  
Vol 455 (2) ◽  
pp. e1-e3
Author(s):  
James S. V. Lally ◽  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Muscle Contractions ◽  
Whole Body ◽  
Glucose Homoeostasis ◽  
Increase Glucose Uptake ◽  
Biochemical Journal ◽  
Complex Events ◽  
Amp Activated Protein Kinase

Skeletal muscle is critical for whole-body glucose homoeostasis. Insulin and muscle contractions induced by exercise can increase glucose uptake through distinct intracellular signalling pathways involving PKB (protein kinase B)/Akt and AMPK (AMP-activated protein kinase) respectively. Whereas the proximal events governing these processes are becoming well understood, less is known about the regulation of the complex events necessary for the control of glucose uptake at the plasma membrane. In recent years, a number of common targets of AMPK and PKB/Akt have emerged as important components controlling glucose uptake, but the necessary phosphorylation events required for the control of glucose uptake have remained more elusive. In the current issue of the Biochemical Journal, Liu et al. identify that PIKfyve, a phosphoinositide phosphate kinase, is required for contraction-stimulated glucose uptake. They demonstrate that AMPK directly phosphorylates PIKfyve at Ser307, the same site as PKB/Akt, and that phosphorylation is increased in response to muscle contractions. These data provide compelling evidence for a new AMPK substrate that converges with PKB/Akt signalling and may be critical for the control of glucose uptake in skeletal muscle.

Autosomal Mutations in Mouse Kidney Epithelial Cells Exposed to High-Energy ProtonsIn Vivoor In Culture

2013 ◽  
Vol 179 (5) ◽  
pp. 521-529 ◽  
Author(s):  
Mitchell S. Turker ◽  
Dmytro Grygoryev ◽  
Cristian Dan ◽  
Bradley Eckelmann ◽  
Michael Lasarev ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
High Energy ◽  
Mouse Kidney ◽  
Kidney Epithelial Cells

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

2010 ◽  
Vol 396 (3) ◽  
pp. 656-661 ◽  
Author(s):  
Lisa Miranda ◽  
Sarah Carpentier ◽  
Anna Platek ◽  
Nusrat Hussain ◽  
Marie-Agnès Gueuning ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Actin Cytoskeleton ◽  
Cytoskeleton Reorganization ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase and the regulation of glucose transport

2006 ◽  
Vol 291 (5) ◽  
pp. E867-E877 ◽  
Author(s):  
Nobuharu Fujii ◽  
Niels Jessen ◽  
Laurie J. Goodyear
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Cardiac Muscle ◽  
Glucose Transport ◽  
Whole Body ◽  
Insulin Resistant ◽  
Treatment And Prevention ◽  
Ampk Activity ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated by acute increases in the cellular [AMP]/[ATP] ratio. In skeletal and/or cardiac muscle, AMPK activity is increased by stimuli such as exercise, hypoxia, ischemia, and osmotic stress. There are many lines of evidence that increasing AMPK activity in skeletal muscle results in increased rates of glucose transport. Although similar to the effects of insulin to increase glucose transport in muscle, it is clear that the underlying mechanisms for AMPK-mediated glucose transport involve proximal signals that are distinct from that of insulin. Here, we discuss the evidence for AMPK regulation of glucose transport in skeletal and cardiac muscle and describe research investigating putative signaling mechanisms mediating this effect. We also discuss evidence that AMPK may play a role in enhancing muscle and whole body insulin sensitivity for glucose transport under conditions such as exercise, as well as the use of the AMPK activator AICAR to reverse insulin-resistant conditions. The identification of AMPK as a novel glucose transport mediator in skeletal muscle is providing important insights for the treatment and prevention of type 2 diabetes.

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