Metformin has adenosine-monophosphate activated protein kinase (AMPK)-independent effects on LPS-stimulated rat primary microglial cultures

Autor: Bożena Gabryel, Bogusław Okopień, Sebastian Liber, Krzysztof Łabuzek
Rok vydání: 2010
Předmět:
Lipopolysaccharides
Adenosine monophosphate
medicine.medical_specialty
endocrine system diseases
Nitrous Oxide
Enzyme Activators
Nitric Oxide Synthase Type II
Inflammation
AMP-Activated Protein Kinases
chemistry.chemical_compound
AMP-activated protein kinase
Internal medicine
medicine
Animals
Hypoglycemic Agents
Rats
Wistar
Protein kinase A
Cells
Cultured
Pharmacology
Arginase
Microglia
biology
Chemistry
NF-kappa B
RNA-Binding Proteins
nutritional and metabolic diseases
AMPK
General Medicine
Ribonucleotides
Aminoimidazole Carboxamide
NFKB1
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Metformin
Rats
Pyrimidines
Endocrinology
medicine.anatomical_structure
Animals
Newborn
biology.protein
Pyrazoles
medicine.symptom
Reactive Oxygen Species
Transcription Factors
medicine.drug
Zdroj: Pharmacological Reports. 62:827-848
ISSN: 1734-1140
DOI: 10.1016/s1734-1140(10)70343-1
Popis: The results of recent studies suggest that metformin, in addition to its efficacy in treating type 2 diabetes, may also have therapeutic potential for the treatment of neuroinflammatory diseases in which reactive microglia play an essential role. However, the molecular mechanisms by which metformin exerts its anti-inflammatory effects remain largely unknown. Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms. In this paper, we attempted to evaluate the effects of metformin on unstimulated and LPS-activated rat primary microglial cell cultures. The presented evidence supports the conclusion that metformin-activated AMPK participates in regulating the release of TNF-α. Furthermore, the effects of metformin on the release of IL-1β, IL-6, IL-10, TGF-β, NO, and ROS as well as on the expression of arginase I, iNOS, NF-κB p65 and PGC-1α were not AMPK-dependent, because pretreatment of LPS-activated microglia with compound C, a pharmacological inhibitor of AMPK, did not reverse the effect of metformin. Based on the present findings, we propose that the shift of microglia toward alternative activation may underlie the beneficial effects of metformin observed in animal models of neurological disorders.
Databáze: OpenAIRE
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