Muscarinic Acetylcholine Receptors Potentiate 5'-Adenosine Monophosphate-Activated Protein Kinase Stimulation and Glucose Uptake Triggered by Thapsigargin-Induced Store-Operated Ca(2+) Entry in Human Neuroblastoma Cells.

Muscarinic Acetylcholine Receptors Potentiate 5'-Adenosine Monophosphate-Activated Protein Kinase Stimulation and Glucose Uptake Triggered by Thapsigargin-Induced Store-Operated Ca(2+) Entry in Human Neuroblastoma Cells. Neurochem Res. 2017 Oct 09;: Authors: Olianas MC, Dedoni S, Onali P Abstract The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of the cellular energy metabolism and may induce either cell survival or death. We previously reported that in SH-SY5Y human neuroblastoma cells stimulation of muscarinic acetylcholine receptors (mAChRs) activate AMPK by triggering store-operated Ca(2+) entry (SOCE). However, whether mAChRs may control AMPK activity by regulating additional mechanisms beyond SOCE remains to be investigated. In the present study we examined the effects of mAChRs on AMPK when SOCE was induced by the sarco-endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. We found that in SH-SY5Y cells depleted of Ca(2+) by thapsigargin, the re-addition Ca(2+) to the medium stimulated AMPK phosphorylation at Thr172, which is required for full kinase activity. This response occurred through SOCE, as it was blocked by either the SOCE modulator 2-aminoethoxydiphephenyl borate, knockdown of the SOCE molecular component STIM1, or inhibition of Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase β (CaMKKβ). In thapsigargin-pretreated cells, stimulation of pharmacologically defined M3 mAC...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research