Rapamycin Induces Mitogen-activated Protein (MAP) Kinase Phosphatase-1 (MKP-1) Expression through Activation of Protein Kinase B and Mitogen-activated Protein Kinase Kinase Pathways

Rastogi, Ruchi; Jiang, Zhongliang; Ahmad, Nisar; Rosati, Rita; Liu, Yusen; Beuret, Laurent; Monks, Robert; Charron, Jean; Birnbaum, Morris J.; Samavati, Lobelia

doi:10.1074/jbc.m113.492702

Cited by 48 publications

(50 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CREB phosphorylation was used as a glucose-induced PKA phosphorylation substrate in ß-cells. Basal phosphorylation was increased by rapamycin as previously observed, 23 but it did not affect glucoseinduced CREB phosphorylation (Fig. 6).…”

Section: Effects Of 3-ma On Pi3supporting

confidence: 87%

Monomethylated-adenines potentiate glucose-induced insulin production and secretion via inhibition of phosphodiesterase activity in rat pancreatic islets

Boland

Alarcón

Ali

et al. 2015

Islets

View full text Add to dashboard Cite

(2015) Monomethylated-adenines potentiate glucose-induced insulin production and secretion via inhibition of phosphodiesterase activity in rat pancreatic islets, Islets, 7:2, e1073435, DOI: 10.1080DOI: 10. /19382014.2015 To link to this article: https://doi.org/10. 1080/19382014.2015 Abbreviations: 3-MA, 3-methyladenine; N6-MA, N6-methyladenine; 9-MA, 9-methyladenine; 1-MA, 1-methyladenine; 7-MA, 7-methyladenine; PKA, protein kinase-A; CREB, cAMP-response element binding protein; 9-CPA, 9-cylopentyladenine; PDE, phosphodiesterase; IBMX, 3-isobutyl-1-methylxanthine; GPR-40, G-protein coupled receptor-40; PLC, phospholipase-C; DAG, diacylglycerol; PKC, protein kinase-C; GLP-1, glucagon-like peptide-1; GIP, gastric inhibitory peptide; MMPX, 8-Methoxymethyl-3-isobutyl-1-methyl xanthine; EHNA, Erythro-9-(2-hydroxy-3-nonyl) adenine; KRBH, Krebs-Ringer bicarbonate buffer; PMSF, phenylmethylsulfonyl fluoride; TLCK, Tosyl-lysyl chloromethylketone; RIA, radioimmunoassay; BCA, bicinchoninic acid; LC3, Microtubule-associated protein-1 light chain-3; mTOR, mammalian Target of Rapamycin; PI3 0 K, phosphatidylinositol-4,5-bisphosphate 3-kinase; PDK-1, Phosphoinositide dependent kinase-1; AMPK, AMP-activated protein kinase.Monomethyladenines have effects on DNA repair, G-protein-coupled receptor antagonism and autophagy. In islet û-cells, 3-methyladenine (3-MA) has been implicated in DNA-repair and autophagy, but its mechanism of action is unclear. Here, the effect of monomethylated adenines was examined in rat islets. 3-MA, N6-methyladenine (N6-MA) and 9-methyladenine (9-MA), but not 1-or 7-monomethylated adenines, specifically potentiated glucose-induced insulin secretion (3-4 fold; p 0.05) and proinsulin biosynthesis (»2-fold; p 0.05). Using 3-MA as a 'model' monomethyladenine, it was found that 3-MA augmented [cAMP] i accumulation (2-3 fold; p 0.05) in islets within 5 minutes. The 3-, N6-and 9-MA also enhanced glucose-induced phosphorylation of the cAMP/protein kinase-A (PKA) substrate cAMP-response element binding protein (CREB). Treatment of islets with pertussis or cholera toxin indicated 3-MA mediated elevation of [cAMP] i was not mediated via G-protein-coupled receptors. Also, 3-MA did not compete with 9-cyclopentyladenine (9-CPA) for adenylate cyclase inhibition, but did for the pan-inhibitor of phosphodiesterase (PDE), 3-isobutyl-1-methylxanthine (IBMX). Competitive inhibition experiments with PDE-isoform specific inhibitors suggested 3-MA to have a preference for PDE4 in islet û-cells, but this was likely reflective of PDE4 being the most abundant PDE isoform in û-cells. In vitro enzyme assays indicated that 3-, N6-and 9-MA were capable of inhibiting most PDE isoforms found in û-cells. Thus, in addition to known inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 0 K)/m Target of Rapamycin (mTOR) signaling, 3-MA also acts as a pan-phosphodiesterase inhibitor in pancreatic û-cells to elevate [cAMP] i and then potentiate glucose-induced insulin secretion and production in parallel.

show abstract

Section: Effects Of 3-ma On Pi3supporting

confidence: 87%

Monomethylated-adenines potentiate glucose-induced insulin production and secretion via inhibition of phosphodiesterase activity in rat pancreatic islets

Boland

Alarcón

Ali

et al. 2015

Islets

View full text Add to dashboard Cite

show abstract

“…However, the mechanism for this Ca 2ϩ -dependent regulation of mTORC1 remains to be elucidated. Rastogi et al (44) found that rapamycin activated both Akt and ERK pathways in macrophages. Another possibility is that the drugs and FKBP12 deficiency increase the activity of Ras at the membrane by promoting its membrane retention and, through the increase in cytosolic Ca 2ϩ , activate guanosine nucleotide exchange factor, RasGRP (Ras guanyl-releasing protein 1).…”

Section: Discussionmentioning

confidence: 99%

Ligands for FKBP12 Increase Ca2+ Influx and Protein Synthesis to Improve Skeletal Muscle Function

Lee

Georgiou

Dagnino-Acosta

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:Rapamycin is a known inhibitor of protein synthesis but also modulates the activity of RyR1. Results: FKBP12 deficiency and low doses of either rapamycin or SLF increase, rather than decrease, protein synthesis and improve muscle function. Conclusion: In skeletal muscle, FKBP12 regulates Ca 2ϩ influx, Ca 2ϩ store refilling, and protein synthesis. Significance: This study lays the groundwork for the development of interventions to slow muscle fatigue.

show abstract

“…Activation of Akt by rapamycin blunts the sensitivity of pro-inflammatory genes to LPS and increases CREB activity (28), and mTOR/Akt signaling additionally suppresses inflammation by inactivating the transcription factor forkhead box O1 (FoxO1) (23). The role of FoxO1 in TLR4 signaling is predominantly pro-inflammatory.…”

mentioning

confidence: 99%

Dynamic Modulation of Innate Immune Response by Varying Dosages of Lipopolysaccharide (LPS) in Human Monocytic Cells

Morris

Gilliam

Button

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Super-low-dose endotoxin causes mild but significant pro-inflammatory skewing. Results: Inhibition of GSK3 or activation of CREB ablates preferential induction of pro-inflammatory genes by super-low-dose LPS. Conclusion: GSK3 is necessary for pro-inflammatory gene induction in response to super-low-dose LPS, acting by activating FoxO1 and suppressing CREB. Significance: Persistent, non-resolving inflammation is a characteristic of many chronic diseases, and this study points toward potential therapeutic targets.

show abstract

Rapamycin Induces Mitogen-activated Protein (MAP) Kinase Phosphatase-1 (MKP-1) Expression through Activation of Protein Kinase B and Mitogen-activated Protein Kinase Kinase Pathways

Cited by 48 publications

References 59 publications

Monomethylated-adenines potentiate glucose-induced insulin production and secretion via inhibition of phosphodiesterase activity in rat pancreatic islets

Monomethylated-adenines potentiate glucose-induced insulin production and secretion via inhibition of phosphodiesterase activity in rat pancreatic islets

Ligands for FKBP12 Increase Ca2+ Influx and Protein Synthesis to Improve Skeletal Muscle Function

Dynamic Modulation of Innate Immune Response by Varying Dosages of Lipopolysaccharide (LPS) in Human Monocytic Cells

Contact Info

Product

Resources

About