scholarly journals AMP-activated protein kinase inhibits Kv1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation

2016 ◽  
Vol 594 (17) ◽  
pp. 4901-4915 ◽  
Author(s):  
Javier Moral-Sanz ◽  
Amira D. Mahmoud ◽  
Fiona A. Ross ◽  
Jodene Eldstrom ◽  
David Fedida ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Pulmonary Arterial ◽  
Amp Activated Protein Kinase ◽  
Channel Currents

scholarly journals AMP-activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside

2007 ◽  
Vol 404 (3) ◽  
pp. 499-507 ◽  
Author(s):  
Bruno Guigas ◽  
Nellie Taleux ◽  
Marc Foretz ◽  
Dominique Detaille ◽  
Fabrizio Andreelli ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Cellular Respiration ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Isolated Rat Hepatocytes ◽  
Amp Activated Protein Kinase ◽  
Isolated Rat ◽  
In Cells

AICA riboside (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) has been extensively used in cells to activate the AMPK (AMP-activated protein kinase), a metabolic sensor involved in cell energy homoeostasis. In the present study, we investigated the effects of AICA riboside on mitochondrial oxidative; phosphorylation. AICA riboside was found to dose-dependently inhibit the oligomycin-sensitive JO2 (oxygen consumption rate) of isolated rat hepatocytes. A decrease in Pi (inorganic phosphate), ATP, AMP and total adenine nucleotide contents was also observed with AICA riboside concentrations >0.1 mM. Interestingly, in hepatocytes from mice lacking both α1 and α2 AMPK catalytic subunits, basal JO2 and expression of several mitochondrial proteins were significantly reduced compared with wild-type mice, suggesting that mitochondrial biogenesis was perturbed. However, inhibition of JO2 by AICA riboside was still present in the mutant mice and thus was clearly not mediated by AMPK. In permeabilized hepatocytes, this inhibition was no longer evident, suggesting that it could be due to intracellular accumulation of Z nucleotides and/or loss of adenine nucleotides and Pi. ZMP did indeed inhibit respiration in isolated rat mitochondria through a direct effect on the respiratory-chain complex I. In addition, inhibition of JO2 by AICA riboside was also potentiated in cells incubated with fructose to deplete adenine nucleotides and Pi. We conclude that AICA riboside inhibits cellular respiration by an AMPK-independent mechanism that likely results from the combined intracellular Pi depletion and ZMP accumulation. Our data also demonstrate that the cellular effects of AICA riboside are not necessarily caused by AMPK activation and that their interpretation should be taken with caution.

scholarly journals Skeletal muscle mitochondrial oxidative phosphorylation function in idiopathic pulmonary arterial hypertension: in vivo and in vitro study

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401876829 ◽  
Author(s):  
Sasiharan Sithamparanathan ◽  
Mariana C. Rocha ◽  
Jehill D. Parikh ◽  
Karolina A. Rygiel ◽  
Gavin Falkous ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Oxidative Phosphorylation ◽  
Arterial Hypertension ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Pulmonary Vessels ◽  
Pulmonary Arterial

Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31P-magnetic resonance spectroscopy (31P-MRS) and laboratory muscle biopsy analysis. 31P-MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.

scholarly journals Intrinsic Protein Kinase Activity in Mitochondrial Oxidative Phosphorylation Complexes

Biochemistry ◽  
2011 ◽  
Vol 50 (13) ◽  
pp. 2515-2529 ◽  
Author(s):  
Darci Phillips ◽  
Angel M. Aponte ◽  
Raul Covian ◽  
Robert S. Balaban
Keyword(s):  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Intrinsic Protein

scholarly journals Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK)

2002 ◽  
Vol 115 (11) ◽  
pp. 2433-2442 ◽  
Author(s):  
Kay Barnes ◽  
Jean C. Ingram ◽  
Omar H. Porras ◽  
L. Felipe Barros ◽  
Emma R. Hudson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Osmotic Stress ◽  
Oxidative Phosphorylation ◽  
Glucose Transporter ◽  
Recombinant Adenovirus ◽  
Surface Concentration ◽  
Cell Types ◽  
Epithelial Cell Line ◽  
Amp Activated Protein Kinase

In the rat liver epithelial cell line Clone 9, the Vmax for glucose uptake is actuely increased by inhibition of oxidative phosphorylation and by osmotic stress. By using a membrane-impermeant photoaffinity labelling reagent together with an isoform-specific antibody, we have, for the first time, provided direct evidence for the involvement of the GLUT1 glucose transporter isoform in this response. Transport stimulation was found to be associated with enhanced accessibility of GLUT1 to its substrate and with photolabelling of formerly `cryptic' exofacial substrate binding sites in GLUT1 molecules. The total amount of cell surface GLUT1 remained constant. The precise mechanism for this binding site `unmasking' is unclear but appears to involve AMP-activated protein kinase: in the current study, osmotic and metabolic stresses were found to result in activation of the α1 isoform of AMP-activated protein kinase, and transport stimulation could be mimicked both by 5-aminoimidazole-4-carboxamide ribonucleoside and by infection of cells with a recombinant adenovirus encoding constitutively active AMP-activated protein kinase. The effect of 5-aminoimidazole-4-carboxamide ribonucleoside, as for metabolic stress, was on the Vmax rather than on the Km for transport and did not affect the cell-surface concentration of GLUT1. The relevant downstream target(s) of AMP-activated protein kinase have not yet been identified, but stimulation of transport by inhibition of oxidative phosphorylation or by 5-aminoimidazole-4-carboxamide ribonucleoside was not prevented by either inhibitors of conventional and novel protein kinase C isoforms or inhibitors of nitric oxide synthase. These enzymes, which have been implicated in stress-regulated pathways in other cell types, are therefore unlikely to play a role in transport regulation by stress in Clone 9 cells.

Sign in / Sign up

Export Citation Format

Share Document