Sargaquinoic acid supports the survival of neuronal PC12D cells in a nerve growth factor-independent manner.
Sargaquinoic acid (designated previously as MC14) was isolated from a marine brown alga Sargassum macrocarpum, and has been found to possess a novel nerve growth factor (NGF)-dependent neurite outgrowth promoting activity in PC12D cells. In this study, we explored the neuroprotective effects of MC14 in terms of its survival supporting, antioxidant and neurite-regenerating activities under NGF deficient or deprived conditions. Intriguingly, MC14 did not only promote the NGF-induced survival support on neuronal PC12D cells, but also significantly abated neuronal PC12D cell death even in the absence of NGF. The pharmacological inhibition of phosphatidylinositol-3 kinase (PI3K) by wortmannin significantly suppressed the survival supporting activity of MC14, whereas the NGF receptor (tyrosine kinase A or TrkA) inhibitor K252a showed no detectable effect on MC14 activity. These results demonstrate that MC14 supports survival of neuronal PC12D cells in an NGF-independent manner, and that PI3K may be required for the neuroprotective activity of MC14. In addition, we have shown that MC14 markedly enhanced neurite-regeneration and protected PC12D cells from hydrogen peroxide (H(2)O(2))-induced oxidative stress. These pharmacological features suggest that MC14 may be a potentially important neuroprotective agent.
Tsang
Chi Kwan
CK
Coastal Bioenvironment Center, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan.
Kamei
Yuto
Y
D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D020932:Nerve Growth Factor / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D000475:Alkenes; D000975:Antioxidants; D016227:Benzoquinones; D018696:Neuroprotective Agents; D016877:Oxidants; C477718:sargaquinoic acid; D020932:Nerve Growth Factor; D006861:Hydrogen Peroxide