Activation of the protein p7OS6K via ERK phosphorylation by cholinergic muscarinic receptors stimulation in human neuroblastoma cells and in mice brain.
Stimulation of cholinergic muscarinic receptors has been shown to provide substantial protection from DNA damage, oxidative stress and mitochondrial impairment, insults that may be encountered by neurons in development, aging, or neurodegenerative diseases. A study recently indicated that the activation of muscarinic receptors in astrocytoma cells modified the expression of the kinase p70S6K involved in the translational control. The translational control is in part regulated by a cascade of phosphorylation affecting proteins of the anti-apoptotic way controlled by mTOR (mammalian target of rapamycin) and the pro-apoptotic way controlled by PKR. The aim of our study was to investigate the effect of cholinergic muscarinic stimulation by an agonist oxotremorine on the anti-apoptotic way of translational control, in human neuroblastoma cells and in mice brain. Our results showed that muscarinic receptor activation significantly increased the expression of phosphorylated p70S6K, eIF4E and ERK without modification of mTOR activity in neuroblastoma cells and in cerebral cortex and hippocampus of mice, suggesting a stimulation of protein synthesis. Our findings support the notion that synaptic activity, through activation of neurotransmitter receptors, can provide substantial support of cellular survival mechanisms and suggest that loss of such synaptic input increases vulnerability to insult-induced programmed cell death.
Deguil
Julie
J
University of Poitiers, Research Group on Brain Aging (EA 3808), Pôle de Biologie Santé, 40 avenue du Recteur Pineau, 86022 Poitiers Cedex, France.
Perault-Pochat
Marie-Christine
MC
Chavant
François
F
Lafay-Chebassier
Claire
C
Fauconneau
Bernard
B
Pain
Stéphanie
S
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases