Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the role of cytosolic phospholipase A2 (PLA2) in the exocytosis of amylase from parotid acinar cells. The exocytosis stimulated by isoproterenol was dose-dependently inhibited by bromoenol lactone (BEL), a potent suicide inhibitor of Ca2+-independent cytosolic PLA2. The IC50 value of BEL was approximately 7 microM. AACOCF3, a selective inhibitor of Ca2+-dependent cytosolic PLA2, did not inhibit the exocytosis at least up to 30 microM. BEL also inhibited amylase release evoked by forskolin and membrane-permeable cAMP, but it did not inhibit cAMP-dependent protein kinase activity. PLA2 activity in parotid acinar cells was found to be predominantly Ca2+-independent, and was strongly inhibited by BEL, whose IC50 value was approximately 2 microM when it was applied to intact acini. Although isoproterenol scarcely enhanced [3H]arachidonic acid release from intact acinar cells, BEL dose-dependently decreased the basal arachidonic acid release to approximately one half of the control value. These results suggest that the cytosolic Ca2+-independent PLA2 activity plays a role in the membrane fusion process of exocytosis in parotid acinar cells.
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PMID:Role of Ca2+-independent phospholipase A2 in exocytosis of amylase from parotid acinar cells. 935 70

Purinoceptor agonists produced potassium currents with the order of potency: ATP > adenosine = ADP = AMP > beta,gamma-methylene ATP, while a small response or no response was induced by 2-methylthio ATP, UTP, or alpha,beta-methylene ATP. The response induced by beta,gamma-methylene ATP was completely inhibited in the presence of alpha,beta-methylene ATP, suggesting that the relevant receptor for these agonists was a P3 purinoceptor. ATP induced currents with a latency of 24 s and the currents were not induced in defolliculated oocytes. The currents were not affected by either the Gi/o-protein inhibitor, pertussis toxin (PTX), or the selective cAMP-dependent protein kinase inhibitor, H-89, or the phospholipase C (PLC) inhibitor, neomycin, or the phospholipase A2 (PLA2) inhibitor, 4-bromophenacyl bromide. The currents were enhanced by the selective protein kinase C (PKC) inhibitor, GF109203X, but otherwise, they were reduced by the potent PKC activator, 12-O-tetradecanoylphorbol-13-acetate. The results of the present study suggest that a P3 purinoceptor in the follicle cell layer of oocytes is involved in activation of potassium channels and that the evoked currents are regulated by PLC/PLA2-independent PKC activation.
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PMID:ATP produces potassium currents via P3 purinoceptor in the follicle cell layer of Xenopus oocytes. 965 60

The activities of enzymes involved in lipid metabolism--phospholipase A2 (PLA2) and phosphatidylethanolamine N-methyltransferase (PE N-MTase)--were found to be differently affected by pre-incubation of rod outer segments (ROS) under protein phosphorylating or dephosphorylating conditions. Exposure to cAMP-dependent protein kinase (PKA), under dark or light conditions, produced a significant increase in PE N-MTase activity, whereas PLA2 activity decreased. Under standard protein kinase C (PKC) phosphorylating conditions in light, PE N-MTase activity was stimulated and PLA2 activity was not affected. When the assays were performed in the dark, both enzymatic activities were unaffected when compared to the corresponding controls. Incubation of ROS membranes in light in the presence of PKC activators phorbol 12,13-dibutyrate (PDBu) and dioctanoylglycerol (DOG) resulted in the same pattern of changes in enzyme activities as described for standard PKC phosphorylating condition. Pre-incubation of membranes with the PKC inhibitor H-7 reduced the stimulation of PDBu on PE N-MTase activity, and had no effect on PLA2 activity in ROS membranes incubated with the phorbol ester. Pre-treatment of isolated ROS with alkaline phosphatase resulted in decreased PE N-MTase activity and produced a significant stimulation of PLA2 activity under dark as well as under light conditions when compared to the corresponding controls. These findings suggest that ROS protein phosphorylation and dephosphorylation modulates PE N-MTase and PLA2 activities in isolated ROS, and that these activities are independently and specifically modulated by particular kinases. Furthermore, dephosphorylation of ROS proteins has the opposite effect to that produced by protein phosphorylation on the enzymes studied.
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PMID:Phosphorylation of rod outer segment proteins modulates phosphatidylethanolamine N-methyltransferase and phospholipase A2 activities in photoreceptor membranes. 985 16

We have previously shown that myogenesis induction by Arg8-vasopressin (AVP) in L6 rat myoblasts involves a sustained stimulation of type 4 cAMP-phosphodiesterase. In this model, we observed that a transient cAMP generation occurs in the minutes following AVP addition. Evidence suggests that cAMP generation is due to the prostaglandins produced in response to AVP binding to V1a receptors and subsequent activation of phospholipase A2. The early cAMP increase was effective in activating cAMP-dependent protein kinase (PKA) and increasing phosphorylation of CREB transcription factor. Inhibition of PKA by compound H89 prior to AVP addition led to a significant reduction of expression of the differentiation marker creatine kinase, whereas H89 added 1-5 h after AVP had no significant effect. Furthermore, PKA inhibition 24 h after the beginning of AVP treatment potentiated differentiation. This shows that both an early activation and a later down-regulation of the cAMP pathway are required for AVP induction of myogenesis. Because phosphodiesterase PDE4D3 overexpressed in L6 cells lost its ability to potentiate AVP-induced differentiation when mutated and rendered insensitive to PKA phosphorylation and activation, we hypothesize that the early cAMP increase is required to trigger the down-regulation of cAMP pathway through stimulation of phosphodiesterase.
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PMID:A bimodal modulation of the cAMP pathway is involved in the control of myogenic differentiation in l6 cells. 1450 85

We investigated the regulation of each intracellular signal transduction system including cyclic AMP (cAMP)-dependent and calcium (Ca2+) messenger systems in bovine adrenal fasciculo-reticularis cells to clarify the exact mode of action of ACTH. Pretreatment with primaquine and quinacrine, which are phospholipase A2 inhibitors, significantly inhibited cortisol production activated by both low and high concentrations of ACTH. Therefore, it seems that metabolites induced by phospholipase A2 are quite essential for cortisol synthesis induced by ACTH, either at low or high concentrations. At low concentrations of ACTH (10(-13)-10(-12) M), significant increases of cytosolic calcium ([Ca2+]i), but not of cAMP, were observed. Calphostin C, a specific protein kinase C inhibitor, apparently suppressed cortisol production activated by low concentrations of ACTH, while H-89, a specific inhibitor of cAMP-dependent protein kinase, did not. These findings suggest that, at physiologically low concentrations, ACTH activates [Ca2+]i and phospholipase A2 without affecting cAMP formation, resulting in an increased biosynthesis of cortisol, partly via protein kinase C-dependent processes. At high concentrations, ACTH (10(-9)-10(-7) M) induced an increase of cAMP and [Ca2+]i. The cortisol production induced by high concentrations of ACTH was significantly inhibited by pretreatment with calphostin C, H-89 and H-7, suggesting the participation of cAMP-dependent protein kinase and protein kinase C systems in the regulation of cortisol production in the presence of high concentrations of ACTH. In conclusion, cytosolic calcium is biphasically enhanced by ACTH, although cAMP accumulation is increased only by high concentrations of ACTH. A phospholipase A2-dependent process may partly play a crucial role in the regulation of cortisol biosynthesis, when stimulated by low and high concentrations of ACTH.
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PMID:Role of calcium messenger systems in ACTH-induced cortisol production in bovine adrenal fasciculo-reticularis cells. 1763 70

The proliferation and adipogenesis of preadipocytes played important roles in the development of adipose tissue and contributed much to the processes of obesity. On the other hand, lipopolysaccharide (LPS), also known as endotoxin, is a key outer membrane component of gram-negative bacteria in the gut microbiota, and has a dominant role in linking inflammation to high-fat diet-induced metabolic syndrome. Studies suggested the potential roles of LPS in hepatic steatosis and in obese mice models. However, the molecular mechanisms underlying LPS-regulated obesity remained largely unknown. Here we reported that LPS stimulated expression of cyosolic phospholipase A2 (cPLA2), one of inflammation regulators of obesity, in the preadipocytes. Pretreatment the inhibitors of JAK2, STAT3, STAT5 or AMPK significantly reduced LPS-increased mRNA and protein expression of cPLA2 together with phosphorylation of JAK2, STAT3, STAT5 and AMPK, separately. Similarly, transfection of siRNA against JAK2 or AMPK abolished expression of cPLA2 and phosphorylation of JAK2 or AMPK together with downregulated expression of JAK2 and AMPK protein. LPS enhanced activation of STAT3 and STAT5 via JAK2-dependent manner in the preadipocytes. Transfection of JAK2 or AMPK siRNA further proofed the independence of JAK2 and AMPK in LPS-treated preadipocytes. In addition, LPS-increased DNA synthesis, cell numbers and cell viability of preadipocytes were attenuated by AACOCF3, AG490, BML-275, cPLA2 siRNA, JAK2 siRNA or AMPK siRNA. Attenuation JAK2/STAT or AMPK-dependent cPLA2 expression reduced LPS-mediated adipogenesis of preadipocytes. Stimulation of arachidonic acid or AMPK activator, A-769662, increased cell numbers and cell viability and promoted differentiation of preadipocytes. Collectively, these results indicated that LPS increased preadipocytes proliferation and adipogenesis via JAK/STAT and AMPK-dependent cPLA2 expression. The mechanisms of LPS-stimulated cPLA2 expression may be a link between bacteria and obesity and provides the molecular basis for preventing metabolic syndrome or hyperplasic obesity.
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PMID:Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. 3066 40


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