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PMID: 11665862 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation.

Journal of molecular neuroscience : MN ·Vol. 17 ·No. 1 ·2001-08-00 ·Pages 45-58

Culmsee C, Monnig J, Kemp BE, Mattson MP

Abstract

Adenosine monophosphate-activated protein kinase (AMPK) is a member of metabolite-sensing kinase family that plays important roles in responses of muscle cells to metabolic stress. AMPK is a heterotrimer of a catalytic alpha subunit (alpha1 or alpha2), and beta (beta1 or beta2) and gamma (gamma1 or gamma2) subunits. Because the brain has a high metabolic rate and is sensitive to changes in the supply of glucose and oxygen, we investigated the expression of AMPK in rat embryonic and adult brain and its role in modifying neuronal survival under conditions of cellular stress. We report that catalytic (alpha1 and alpha2) and noncatalytic (beta2 and gamma1) subunits of AMPK are present at high levels in embryonic hippocampal neurons in vivo and in cell culture. In the adult rat brain, the catalytic subunits alpha1 and alpha2 are present in neurons throughout the brain. The AMPK-activating agent AICAR protected hippocampal neurons against death induced by glucose deprivation, chemical hypoxia, and exposure to glutamate and amyloid beta-peptide. Suppression of levels of the AMPK alpha1 and alpha2 subunits using antisense technology resulted in enhanced neuronal death following glucose deprivation, and abolished the neuroprotective effect of AICAR. These findings suggest that AMPK can protect neurons against metabolic and excitotoxic insults relevant to the pathogenesis of several different neurodegenerative conditions.

MeSH Terms
AMP-Activated Protein Kinases Aminoimidazole Carboxamide/analogs & derivatives,pharmacology Animals Apoptosis/physiology Brain/cytology,embryology,enzymology,growth & development Cell Survival/physiology Cells, Cultured Glucose/metabolism Hypoglycemic Agents/pharmacology Immunohistochemistry Male Multienzyme Complexes/chemistry,genetics,metabolism Neurons/cytology,drug effects,enzymology,physiology Neuroprotective Agents/pharmacology Oligonucleotides, Antisense/metabolism Protein Serine-Threonine Kinases/chemistry,genetics,metabolism Protein Subunits Rats Rats, Sprague-Dawley Ribonucleotides/pharmacology Triazines/pharmacology Triazoles/pharmacology Xanthines/pharmacology
Chemicals
Hypoglycemic Agents Multienzyme Complexes Neuroprotective Agents Oligonucleotides, Antisense Protein Subunits Ribonucleotides Triazines Triazoles Xanthines ZM 241385 Aminoimidazole Carboxamide 1,3-dipropyl-8-cyclopentylxanthine Protein Serine-Threonine Kinases AMP-Activated Protein Kinases AICA ribonucleotide Glucose
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Culmsee C
Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
Monnig J
Kemp B E
Mattson M P
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Article Info
Journal
Journal of molecular neuroscience : MN
Abbr.
J Mol Neurosci
ISSN
0895-8696
DOI
10.1385/JMN:17:1:45
Published
2001-08-00
Pages
45-58
Language
English
Region
United States
NLM ID
9002991
Subset
IM
External Links
PubMed source DOI: 10.1385/JMN:17:1:45 View journal details
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