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AMPK-Regulated Astrocytic Lactate Shuttle Plays a Non-Cell-Autonomous Role in Neuronal Survival.

التفاصيل البيبلوغرافية
العنوان: AMPK-Regulated Astrocytic Lactate Shuttle Plays a Non-Cell-Autonomous Role in Neuronal Survival.
المؤلفون: Muraleedharan R; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Gawali MV; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Tiwari D; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Sukumaran A; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Oatman N; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Anderson J; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Nardini D; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Bhuiyan MAN; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Tkáč I; Center for Magnetic Resonance Research, University of Minnesota, 2450 Riverside Ave., Minneapolis, MN 55455, USA., Ward AL; Pathology and Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA., Kundu M; Pathology and Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA., Waclaw R; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA., Chow LM; Hematology/Oncology, Dayton Children's Hospital, 1 Childrens Plaza, Dayton, OH 45404, USA., Gross C; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA., Rao R; Pediatrics, University of Minnesota, 2450 Riverside Ave., Minneapolis, MN 55455, USA., Schirmeier S; Institute for Neuro-and Behavioral Biology, University of Münster, Badestrasse 9, 48149 Münster, Germany., Dasgupta B; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: biplab.dasgupta@cchmc.org.
المصدر: Cell reports [Cell Rep] 2020 Sep 01; Vol. 32 (9), pp. 108092.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: AMP-Activated Protein Kinases/*metabolism , Astrocytes/*metabolism , Lactic Acid/*metabolism , Neurons/*metabolism, Animals ; Cell Death ; Humans ; Mice
مستخلص: Lactate is used as an energy source by producer cells or shuttled to neighboring cells and tissues. Both glucose and lactate fulfill the bioenergetic demand of neurons, the latter imported from astrocytes. The contribution of astrocytic lactate to neuronal bioenergetics and the mechanisms of astrocytic lactate production are incompletely understood. Through in vivo 1 H magnetic resonance spectroscopy, 13 C glucose mass spectroscopy, and electroencephalographic and molecular studies, here we show that the energy sensor AMP activated protein kinase (AMPK) regulates neuronal survival in a non-cell-autonomous manner. Ampk-null mice are deficient in brain lactate and are seizure prone. Ampk deletion in astroglia, but not neurons, causes neuronal loss in both mammalian and fly brains. Mechanistically, astrocytic AMPK phosphorylated and destabilized thioredoxin-interacting protein (TXNIP), enabling expression and surface translocation of the glucose transporter GLUT1, glucose uptake, and lactate production. Ampk loss in astrocytes causes TXNIP hyperstability, GLUT1 misregulation, inadequate glucose metabolism, and neuronal loss.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
معلومات مُعتمدة: P41 EB027061 United States EB NIBIB NIH HHS; T32 ES007250 United States ES NIEHS NIH HHS; R01 NS075291 United States NS NINDS NIH HHS; P30 NS076408 United States NS NINDS NIH HHS; R01 GM132231 United States GM NIGMS NIH HHS; R01 NS099162 United States NS NINDS NIH HHS; R01 MH115058 United States MH NIMH NIH HHS; P41 EB015894 United States EB NIBIB NIH HHS; R01 NS092705 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: AMP kinase; GLUT1; TXNIP; astrocyte-neuron lactate shuttle; brain metabolism; glucose flux; glycolysis; proton spectroscopy
المشرفين على المادة: 33X04XA5AT (Lactic Acid)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
تواريخ الأحداث: Date Created: 20200903 Date Completed: 20210528 Latest Revision: 20220208
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7531170
DOI: 10.1016/j.celrep.2020.108092
PMID: 32877674
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2020.108092