Orexins protect neuronal cell cultures against hypoxic stress: an involvement of Akt signaling.
Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress. We report the first evidence that orexins A and B stimulated Akt in cortical neurons in a concentration- and time-dependent manner. Orexin B more potently than orexin A increased Akt phosphorylation, but the maximal effect of both peptides on the kinase activation was very similar. Next, cultured cortical neurons were challenged with cobalt chloride, an inducer of reactive oxygen species and hypoxia-mediated signaling pathways. Under conditions of chemical hypoxia, orexins potently increased neuronal viability and protected cortical neurons against oxidative stress. Our results also indicate that Akt kinase plays an important role in the pro-survival effects of orexins in neurons, which implies a possible mechanism of the orexin-induced neuroprotection.
Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232, Łódź, Poland.
Paulina
P
Sokołowska
Anna
A
Urbańska
Kaja
K
Biegańska
Waldemar
W
Wagner
Wojciech
W
Ciszewski
Magdalena
M
Namiecińska
Jolanta B
JB
Zawilska
D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003035:Cobalt / Q000633:toxicity; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000068797:Orexins; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D000068797:Orexins; D017382:Reactive Oxygen Species; D003035:Cobalt; D051057:Proto-Oncogene Proteins c-akt; C018021:cobaltous chloride