Korean J Physiol Pharmacol.  2007 Apr;11(2):37-43.

A1 Receptor-mediated Protection against Amyloid Beta-induced Injury in Human Neuroglioma Cells

• Cho YW
• Jung HJ
• Kim YK
• Woo JS

Abstract

Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against Abeta-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and Abeta25~35 were employed to produce an experimental Abeta-induced glial cell injury model. Adenosine significantly prevented Abeta-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by A1 receptors. Adenosine attenuated Abeta-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented Abeta-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive K+ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against Abeta-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochondrial functional integrity through opening of the mitochondrial ATP-sensitive K+ channels.

Keyword

Adenosine; A1 receptor; Amyloid beta peptide; Glial cell; Apoptosis

MeSH Terms

Adenosine
Adenosine Triphosphate
Amyloid beta-Peptides
Amyloid*
Apoptosis
Caspase 9
Cell Death
Cell Line
Central Nervous System
Cytochromes c
Cytoprotection
Cytosol
Humans*
Myocardium
Neuroglia
Permeability
Receptors, Purinergic P1
Adenosine
Adenosine Triphosphate
Amyloid
Amyloid beta-Peptides
Caspase 9
Cytochromes c
Receptors, Purinergic P1