scholarly journals Fatty Acids Regulate Porcine Reproductive and Respiratory Syndrome Virus Infection via the AMPK-ACC1 Signaling Pathway

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1145 ◽  
Author(s):  
Siwen Long ◽  
Yanrong Zhou ◽  
Dongcheng Bai ◽  
Wanjun Hao ◽  
Bohan Zheng ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adenosine Monophosphate ◽  
Respiratory Syndrome Virus ◽  
Biosynthesis Pathway ◽  
Acetyl Coa Carboxylase ◽  
Inactive Form ◽  
Antiviral Targets ◽  
Amp Activated Protein Kinase ◽  
New Evidence ◽  
Rate Limiting

Lipids play a crucial role in the replication of porcine reproductive and respiratory syndrome virus (PRRSV), a porcine virus that is endemic throughout the world. However, little is known about the effect of fatty acids (FAs), a type of vital lipid, on PRRSV infection. In this study, we found that treatment with a FA biosynthetic inhibitor significantly inhibited PRRSV propagation, indicating the necessity of FAs for optimal replication of PRRSV. Further study revealed that 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), a key kinase antagonizing FA biosynthesis, was strongly activated by PRRSV and the pharmacological activator of AMPK exhibited anti-PRRSV activity. Additionally, we found that acetyl-CoA carboxylase 1 (ACC1), the first rate-limiting enzyme in the FA biosynthesis pathway, was phosphorylated (inactive form) by PRRSV-activated AMPK, and active ACC1 was required for PRRSV proliferation, suggesting that the PRRSV infection induced the activation of the AMPK–ACC1 pathway, which was not conducive to PRRSV replication. This work provides new evidence about the mechanisms involved in host lipid metabolism during PRRSV infection and identifies novel potential antiviral targets for PRRSV.

Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Moderate Intensity ◽  
Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

scholarly journals Regulation of acetyl-CoA carboxylase in rat mammary gland. Effects of starvation and of insulin and prolactin deficiency on the fraction of the enzyme in the active form in vivo

1982 ◽  
Vol 204 (1) ◽  
pp. 273-280 ◽  
Author(s):  
Elizabeth M. McNeillie ◽  
Victor A. Zammit
Keyword(s):  
Mammary Gland ◽  
Enzyme Activities ◽  
Enzyme Concentration ◽  
Acetyl Coa Carboxylase ◽  
Initial Activity ◽  
Acetyl Coa ◽  
Activity Ratios ◽  
Rat Mammary Gland ◽  
Rate Limiting

The ‘initial’ (I), endogenous phosphatase-activated (A) and citrate-activated (C) activities of acetyl-CoA carboxylase were measured in mammary-gland extracts of pregnant and lactating rats. There was a 10-fold increase in the A and C enzyme activities in the transition from early to peak lactation [cf. data of Mackall & Lane (1977) Biochem. J.162, 635–642], but there was no significant increase in the ratio of the initial activity to the A and C activities of the enzyme. Starvation (24h) or short-term (3h) streptozotocin-induced diabetes both resulted in a 40% decrease in I/A and I/C activity ratios. In starvation this was accompanied by a decrease in the absolute values of the A and C activities such that the initial activity in mammary glands of starved animals was 45% that in glands from fed animals. Insulin treatment of starved or diabetic animals 60min before killing increased the I activity without affecting the A or C enzyme activities. Removal of the pups for 24h from animals in peak lactation (weaning) resulted in a marked but similar decrease in all three activities such that, although the initial activity was only 10% of that in suckled animals, the I/A and I/C activity ratios remained high and unaltered. Inhibition of prolactin secretion by injection of 2-bromo-α-ergocryptine gave qualitatively similar results to those during weaning. Simultaneous administration of ovine prolactin completely prevented the effects of bromoergocryptine. It is suggested that the initial activity of acetyl-CoA carboxylase in rat mammary gland is regulated by at least two parallel mechanisms: (i) an acute regulation of the proportion of the enzyme in the active state and (ii) a longer-term modulation of enzyme concentration in the gland. Insulin appeared to mediate its acute effects through mechanism (i), whereas prolactin had longer-term effects on enzyme concentration in the gland. A comparison of initial enzyme activities (I) obtained in the present study with rates of lipogenesis measured in vivo [Agius & Williamson (1980) Biochem. J.192, 361–364; Munday & Williamson (1981) Biochem. J.196, 831–837] gave good agreement between the two sets of data for all conditions studied except for 24h-starved and streptozotocin-diabetic animals. It is suggested that acetyl-CoA carboxylase activity is rate-limiting for lipogenesis in the mammary gland in normal, fed, suckled or weaned animals but that in starved and short-term diabetic animals changes in the activity of the enzyme by covalent modification alone may not be sufficient to maintain the enzyme in its rate-limiting role.

Effect of phosphorylation by AMP-activated protein kinase on palmitoyl-CoA inhibition of skeletal muscle acetyl-CoA carboxylase

2005 ◽  
Vol 98 (4) ◽  
pp. 1221-1227 ◽  
Author(s):  
D. S. Rubink ◽  
W. W. Winder
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Oxidation Rates ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) has previously been demonstrated to phosphorylate and inactivate skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, an inhibitor of carnitine palmitoyltransferase 1 and fatty acid oxidation. Contraction-induced activation of AMPK with subsequent phosphorylation/inactivation of ACC has been postulated to be responsible in part for the increase in fatty acid oxidation that occurs in muscle during exercise. These studies were designed to answer the question: Does phosphorylation of ACC by AMPK make palmitoyl-CoA a more effective inhibitor of ACC? Purified rat muscle ACC was subjected to phosphorylation by AMPK. Activity was determined on nonphosphorylated and phosphorylated ACC preparations at acetyl-CoA concentrations ranging from 2 to 500 μM and at palmitoyl-CoA concentrations ranging from 0 to 100 μM. Phosphorylation resulted in a significant decline in the substrate saturation curve at all palmitoyl-CoA concentrations. The inhibitor constant for palmitoyl-CoA inhibition of ACC was reduced from 1.7 ± 0.25 to 0.85 ± 0.13 μM as a consequence of phosphorylation. At 0.5 mM citrate, ACC activity was reduced to 13% of control values in response to the combination of phosphorylation and 10 μM palmitoyl-CoA. Skeletal muscle ACC is more potently inhibited by palmitoyl-CoA after having been phosphorylated by AMPK. This may contribute to low-muscle malonyl-CoA values and increasing fatty acid oxidation rates during long-term exercise when plasma fatty acid concentrations are elevated.

scholarly journals The protective effect of the PDE-4 inhibitor rolipram on intracerebral haemorrhage is associated with the cAMP/AMPK/SIRT1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiao-Liu Dong ◽  
Yan-Hui Wang ◽  
Jing Xu ◽  
Nan Zhang
Keyword(s):  
Mouse Model ◽  
Protective Effect ◽  
Intracerebral Haemorrhage ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Pathological Process ◽  
Silent Information Regulator 1 ◽  
Sirt1 Inhibitor ◽  
Amp Activated Protein Kinase

AbstractRolipram specifically inhibits phosphodiesterase (PDE) 4, thereby preventing inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to play a neuroprotective role in some central nervous system (CNS) diseases. However, the role of PDE4 and the potential protective effect of rolipram on the pathophysiological process of intracerebral haemorrhage (ICH) are still not entirely clear. In this study, a mouse model of ICH was established by the collagenase method. Rolipram reduced brain oedema, blood–brain barrier (BBB) leakage, neuronal apoptosis and inflammatory cytokine release and improved neurological function in our mouse model of ICH. Moreover, rolipram increased the levels of cAMP and silent information regulator 1 (SIRT1) and upregulated the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, these effects of rolipram could be reversed by the SIRT1 inhibitor sirtinol. In conclusion, rolipram can play a neuroprotective role in the pathological process of ICH by activating the cAMP/AMPK/SIRT1 pathway.

scholarly journals Glucagon Activates the AMP‐Activated Protein Kinase/Acetyl‐CoA Carboxylase Pathway in Adipocytes

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
I‐Chen Peng ◽  
Zhen Chen ◽  
Pang‐Hung Hsu ◽  
Mei‐I Su ◽  
Ming‐Daw Tsai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Amp Activated Protein Kinase

scholarly journals Toxic Mechanisms of Aryloxyphenoxypropionates in Target and Non-target Organisms

2019 ◽  
pp. 1-11
Author(s):  
Ayokanmi Ore ◽  
Ebenezer Tunde Olayinka
Keyword(s):  
Membrane Lipids ◽  
Lipid Synthesis ◽  
Oxygen Species ◽  
Acetyl Coa Carboxylase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Major Toxicity ◽  
Pharmacokinetic Properties ◽  
Entire Plant ◽  
Rate Limiting

Herbicides are substances used to control unwanted plants-weeds. They can be classified into several classes by mechanism of action. This review describes the members of aryloxyphenoxypropionate herbicides, their pharmacokinetic properties, metabolism and their mechanism of phytotoxicity in target weeds as well as in non-target organisms. Two major toxicity mechanisms are described. The first is by inhibition of lipid synthesis. This is achieved by inhibiting the rate limiting step of lipid biosynthesis catalyzed by acetyl CoA carboxylase. The second mechanism is by induction of oxidative stress. This is achieved by generation of reactive oxygen species which in excess can cause oxidative damage to macromolecules and cellular structures especially the membrane lipids. Loss of vital membrane lipids alters the fluidity of membrane, loss of cellular contents and eventually cell death and death of the entire plant.

scholarly journals Ωρίμανση ωοκυττάρων in vitro

2012 ◽  
Author(s):  
Ολυμπία Πικίου
Keyword(s):  
Protein Kinase ◽  
Tuberous Sclerosis ◽  
Adenosine Triphosphate ◽  
Tuberous Sclerosis Complex ◽  
Adenosine Monophosphate ◽  
Amp Activated Protein Kinase

Η μετφορμίνη, ένα παράγωγο της διγουανίδης, χρησιμοποιείται ως θεραπεία του σακχαρώδη διαβήτη τύπου 2 και στη θεραπεία του PCOS. Οι κύριες δράσεις της μετφορμίνης είναι η αναστολή της παραγωγής γλυκόζης από το ήπαρ και η μείωση της αντίστασης στην ινσουλίνη από περιφερικούς ιστούς, οδηγώντας σε αυξημένη πρόσληψη και χρήση της γλυκόζης από τους σκελετικούς μυς. Ο κύριος διαμεσολαβητής της δράσης της μετφορμίνης είναι η AMPK [AMP-activated protein kinase: πρωτεϊνική κινάση που ενεργοποιείται από την AMP (μονοφωσφορική αδενοσίνη)]. Η AMPK είναι ο κεντρικός αισθητήρας των επιπέδων ενέργειας στο κύτταρο, ο οποίος ανταποκρίνεται στην αύξηση του λόγου AMP/ATP (adenosine monophosphate/adenosine triphosphate: μονοφωσφορική/τριφωσφορική αδενοσίνη). Μελέτες σε ωοκύτταρα βοοειδών έχουν δείξει ότι η ενεργοποίηση της AMPK από τη μετφορμίνη σε υψηλές συγκεντρώσεις της τάξεως των mM ελέγχει την πυρηνική ωρίμανση. Το TSC2 (tuberous sclerosis complex 2: σύμπλεγμα οζώδους σκλήρυνσης 2) έχει αναγνωριστεί ως ο κατωφερής στόχος της AMPK. Σκοπός της παρούσης μελέτης ήταν η διερεύνηση της επίδρασης χαμηλών συγκεντρώσεων μετφορμίνης (1nM-10μΜ) (i) στη δημιουργία εμβρύων βοοειδών από συμπλέγματα ωοκυττάρου-ωοφόρου δίσκου, (ii) το ρυθμό διαίρεσης των εμβρύων και, (iii) την πιθανή ενεργοποίηση του TSC2 μέσω της AMPK. Τα συμπλέγματα ωοκυττάρου-ωοφόρου δίσκου ωρίμαζαν in vitro, γονιμοποιούνταν με αναβιωμένα σπερματοζωάρια ταύρου και τα ζυγωτά καλλιεργούνταν συνολικά για 72 ώρες μετά τη σπερματέγχυση. Η μετφορμίνη χορηγήθηκε σε όλα τα στάδια της παραγωγής των εμβρύων ή μόνο κατά το στάδιο της γονιμοποίησης. Προκειμένου να διερευνηθεί η παρουσία της TSC2 κατά τα πρώτα στάδια ανάπτυξης των εμβρύων και η πιθανή ενεργοποίηση του μορίου αυτού μέσω της AMPK πραγματοποιήθηκαν πειράματα ανοσοφθορισμού. Σύμφωνα με τα αποτελέσματα μας, η χορήγηση της μετφορμίνης είχε δοσο-εξαρτώμενη επίδραση στο ρυθμό διαίρεσης των εμβρύων. Συγκεκριμένα, παρουσία μετφορμίνης σε όλα τα στάδια της in vitro παραγωγής εμβρύων σε συγκέντρωση 1μΜ και 10μΜ ή μόνο στο στάδιο της in vitro γονιμοποίησης σε συγκέντρωση 0,1μΜ και 10μΜ, το ποσοστό των εμβρύων που έφτασαν στο στάδιο των ≥8-κυττάρων παρουσίασε στατιστικώς σημαντική μείωση, σε σχέση με αυτό της ομάδας ελέγχου. Η μείωση αυτή στο ποσοστό των εμβρύων ≥8-κυττάρων συνοδεύτηκε από αύξηση του ποσοστού των εμβρύων 2-κυττάρων. Η μετφορμίνη δεν είχε καμία επίδραση στο ποσοστό των ωοκυττάρων που εξελίχθηκαν σε έμβρυα. Σύμφωνα με τα αποτελέσματα μας, το TSC2 εκφράζεται κατά τα πρώτα στάδια ανάπτυξης των εμβρύων βοοειδών. Επιπλέον διαπιστώθηκε ότι, η χορήγηση 10μΜ μετφορμίνης είτε σε όλα τα στάδια της in vitro παραγωγής εμβρύων ή μόνο κατά το στάδιο της in vitro γονιμοποίησης είχε ως αποτέλεσμα την ενεργοποίηση του TSC2 μέσω της AMPK. Συγκεκριμένα διαπιστώθηκε ότι, τα επίπεδα του φωσφορυλιωμένου TSC2, μετά τη χορήγηση μετφορμίνης, αντιστοιχούν στην ολική ποσότητα TSC2 πρωτεΐνης στα κύτταρα γεγονός που προκύπτει τόσο από την αύξηση της PhosphoS1387-TSC2-ανοσοδραστικότητας όσο και από την αύξηση του λόγου PhosphoS1387-TSC2 : ολική TSC2 η οποία παρατηρήθηκε. Τα αποτελέσματα της παρούσης διατριβής υποδεικνύουν για πρώτη φορά ότι, η μετφορμίνη δεν έχει καμία επίδραση στο ποσοστό των ωοκυττάρων που εξελίσσονται σε έμβρυα και κατά συνέπεια δεν επηρεάζει την ωρίμανση των ωοκυττάρων όταν χορηγείται σε συγκεντρώσεις της τάξεως των μM. Εντούτοις, η μετφορμίνη σε αυτές τις συγκεντρώσεις έχει αρνητική δοσο-εξαρτώμενη επίδραση στο ρυθμό διαίρεσης των εμβρύων βοοειδών. Η δράση αυτή της μετφορμίνης στο ρυθμό διαίρεσης των εμβρύων είναι η ίδια είτε το φάρμακο χορηγείται καθ' όλη τη διάρκεια της in vitro παραγωγής των εμβρύων είτε μόνο κατά το στάδιο της in vitro γονιμοποίησης. Επιπλέον, δεδομένου ότι η μετφορμίνη είναι ενεργοποιητής της ΑΜΡΚ, τα αποτελέσματα μας σηματοδοτούν τη σπουδαιότητα της ρύθμισης της δραστηριότητας της ΑΜΡΚ κατά τα πρώτα στάδια ανάπτυξης των εμβρύων και δείχνουν ότι κάθε μεταβολή των επιπέδων δραστηριότητας του ενζύμου αυτού μπορεί να έχει αρνητική επίδραση στην ανάπτυξη των εμβρύων. Τέλος, από τα αποτελέσματα μας μπορεί να συναχθεί ότι το μοριακό μονοπάτι το οποίο εμπλέκεται στη μείωση του ρυθμού διαίρεσης των εμβρύων από τη μετφορμίνη περιλαμβάνει την ενεργοποίηση του TSC2 από την ΑΜΡΚ.

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