scholarly journals Decreased rates of cerebral protein synthesis measured in vivo in a mouse model of Tuberous Sclerosis Complex: unexpected consequences of reduced tuberin

2018 ◽  
Vol 145 (5) ◽  
pp. 417-425 ◽  
Author(s):  
Rachel Michelle Saré ◽  
Tianjian Huang ◽  
Tom Burlin ◽  
Inna Loutaev ◽  
Carolyn Beebe Smith
Keyword(s):  
Protein Synthesis ◽  
Mouse Model ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cerebral Protein Synthesis ◽  
Unexpected Consequences

scholarly journals Therapeutic Trial of Metformin and Bortezomib in a Mouse Model of Tuberous Sclerosis Complex (TSC)

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31900 ◽  
Author(s):  
Neil Auricchio ◽  
Izabela Malinowska ◽  
Reuben Shaw ◽  
Brendan D. Manning ◽  
David J. Kwiatkowski
Keyword(s):  
Mouse Model ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Therapeutic Trial

scholarly journals Metabolomic studies identify changes in transmethylation and polyamine metabolism in a brain-specific mouse model of tuberous sclerosis complex

2018 ◽  
Vol 27 (12) ◽  
pp. 2113-2124 ◽  
Author(s):  
James McKenna ◽  
David Kapfhamer ◽  
Jason M Kinchen ◽  
Brandi Wasek ◽  
Matthew Dunworth ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Polyamine Metabolism

Abstract 5510: Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex.

2013 ◽  
Author(s):  
Shaowei Li ◽  
Ji-an Wang ◽  
Rajesh L. Thangapazham ◽  
Peter Klover ◽  
Joel Moss ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tuberous Sclerosis ◽  
Tumor Cells ◽  
Tuberous Sclerosis Complex ◽  
Skin Tumor ◽  
Xenograft Mouse Model

scholarly journals In vivo optical properties of cortical tubers in children with tuberous sclerosis complex (TSC): a preliminary investigation

Epilepsia ◽  
2011 ◽  
Vol 52 (9) ◽  
pp. 1699-1704 ◽  
Author(s):  
Sanghoon Oh ◽  
Tara Stewart ◽  
Ian Miller ◽  
Sanjiv Bhatia ◽  
John Ragheb ◽  
...  
Keyword(s):  
Optical Properties ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Preliminary Investigation ◽  
Cortical Tubers

scholarly journals Do We Have a Cure for Tuberous Sclerosis Complex?

2008 ◽  
Vol 8 (6) ◽  
pp. 159-162 ◽  
Author(s):  
Peter B. Crino
Keyword(s):  
Tuberous Sclerosis ◽  
Task Performance ◽  
Mouse Models ◽  
Tuberous Sclerosis Complex ◽  
Protein Function ◽  
Learning Task ◽  
Neurological Manifestations ◽  
Intractable Seizures

The recent development of several mouse models for tuberous sclerosis complex (TSC) provides in vivo systems to test new therapies for the neurological manifestations of TSC. Rapamycin is known to antagonize the effects of loss of TSC protein function in vitro and in mouse TSC models, rapamycin can prevent seizures and improve learning task performance. These findings provide new hope for TSC patients suffering from intractable seizures and possibly, for those with autism and cognitive disabilities.

scholarly journals Effects of chronic inhibition of phosphodiesterase-4D on behavior and regional rates of cerebral protein synthesis in a mouse model of fragile X syndrome

2021 ◽  
pp. 105485
Author(s):  
Michael Rosenheck ◽  
Carrie Sheeler ◽  
Rachel Michelle Saré ◽  
Mark E. Gurney ◽  
Carolyn Beebe Smith
Keyword(s):  
Protein Synthesis ◽  
Mouse Model ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Phosphodiesterase 4D ◽  
Cerebral Protein Synthesis

scholarly journals Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2)

2005 ◽  
Vol 388 (3) ◽  
pp. 973-984 ◽  
Author(s):  
Mark ROLFE ◽  
Laura E. McLEOD ◽  
Phillip F. PRATT ◽  
Christopher G. PROUD
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mammalian Target Of Rapamycin ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Erk Activation ◽  
Mitogen Activated Protein

The hypertrophic Gq-protein-coupled receptor agonist PE (phenylephrine) activates protein synthesis. We showed previously that activation of protein synthesis by PE requires MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] and mTOR (mammalian target of rapamycin). However, it remained unclear whether ERK activation was required and which downstream components were involved in activating mTOR and protein synthesis. Using an adenovirus encoding the MKP3 (MAPK phosphatase 3) to inhibit ERK activity, we demonstrate that ERK is essential for the activation of protein synthesis by PE. Activation and phosphorylation of S6K1 (ribosomal protein S6 kinase 1) and phosphorylation of eIF4E (eukaryotic initiation factor 4E)-binding protein (both are mTOR targets) were also inhibited by MKP3, suggesting that ERK is also required for the activation of mTOR signalling. PE stimulation of cardiomyocytes induced the phosphorylation of TSC2 (tuberous sclerosis complex 2), a negative regulator of mTOR activity. TSC2 was phosphorylated only weakly at Thr1462, but phosphorylated at additional sites within the sequence RXRXX(S/T). This differs from the phosphorylation induced by insulin, indicating that MEK/ERK signalling targets distinct sites in TSC2. This phosphorylation may be mediated by p90RSK (90 kDa ribosomal protein S6K), which is activated by ERK, and appears to involve phosphorylation at Ser1798. Activation of protein synthesis by PE is partially insensitive to the mTOR inhibitor rapamycin. Inhibition of the MAPK-interacting kinases by CGP57380 decreases the phosphorylation of eIF4E and PE-induced protein synthesis. Moreover, CGP57380+rapamycin inhibited protein synthesis to the same extent as blocking ERK activation, suggesting that MAPK-interacting kinases and regulation of mTOR each contribute to the activation of protein synthesis by PE in cardiomyocytes.

scholarly journals In vivo Cerebral Protein Synthesis Rates with Leucyl-Transfer RNA Used as a Precursor Pool: Determination of Biochemical Parameters to Structure Tracer Kinetic Models for Positron Emission Tomography

1989 ◽  
Vol 9 (4) ◽  
pp. 429-445 ◽  
Author(s):  
Randy E. Keen ◽  
Jorge R. Barrio ◽  
Sung-Cheng Huang ◽  
Randall A. Hawkins ◽  
Michael E. Phelps
Keyword(s):  
Positron Emission Tomography ◽  
Protein Synthesis ◽  
Bolus Injection ◽  
Emission Tomography ◽  
Precursor Pool ◽  
Leucine Oxidation ◽  
Positron Emission ◽  
Tissue Compartments ◽  
Cerebral Protein Synthesis

Leucine oxidation and incorporation into proteins were examined in the in vivo rat brain to determine rates and compartmentation of these processes for the purpose of structuring mathematical compartmental models for the noninvasive estimation of in vivo human cerebral protein synthesis rates (CPSR) using positron emission tomography (PET). Leucine specific activity (SA) in arterial plasma and intracellular free amino acids, leucyl-tRNA, α-ketoisocaproic acid (KIC), and protein were determined in whole brain of the adult rat during the first 35 min after intravenous bolus injection of l-[1-14C]leucine. Incorporation of leucine into proteins accounted for 90% of total brain radioactivity at 35 min. The lack of [14C]KIC buildup indicates that leucine oxidation in brain is transaminase limited. Characteristic specific activities were maximal between 0 to 2 min after bolus injection with subsequent decline following the pattern: plasma leucine ≥ leucyl-tRNA ≈ KIC > intracellular leucine. The time integral of leucine SA in plasma was about four times that of tissue leucine and twice those of leucyl-tRNA and KIC, indicating the existence of free leucine, leucyl-tRNA, and KIC tissue compartments, communicating directly with plasma, and separate secondary free leucine, leucyl-tRNA, and KIC tissue compartments originating in unlabeled leucine from proteolysis. Therefore, a relatively simple model configuration based on the key assumptions that (a) protein incorporation and catabolism proceed from a precursor pool communicating with the plasma space, and (b) leucine catabolism is transaminase limited is justified for the in vivo assessment of CPSR from exogenous leucine sources using PET in humans.

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