The neuroprotective adenosine-activated signal transduction pathway involves activation of phospholipase C.
We have demonstrated before that exposure of neuronal cultures to poisoning by iodoacetic acid (IAA) followed by "reperfusion" (IAA-R insult), results in severe cytotoxicity, which could be markedly attenuated by prior activation of the adenosine A1 receptors. We also have demonstrated that adenosine activates a signal transduction pathway (STP), which involves activation of PKC epsilon and opening of KATP channels. Here, we provide proof for the involvement also of phospholipase C (PLC) in the neuronal protective adenosine-activated STP. R-PIA, a specific A1 adenosine receptor agonist, was found to enhance neuronal PLC activity and protect against the IAA-R insult. The PLC inhibitor U73122, abrogated both R-PIA-induced effects. These results demonstrate that activation of PLC is a vital step in the neuronal protective adenosine-induced STP.
Rogel
A
A
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bromberg
Y
Y
Sperling
O
O
Zoref-Shani
E
E
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019807:Iodoacetic Acid / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D004963:Estrenes; D018696:Neuroprotective Agents; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010738:Type C Phospholipases; D000241:Adenosine; D019807:Iodoacetic Acid