Fermented Antrodia cinnamomea extract protects rat PC12 cells from serum deprivation-induced apoptosis: the role of the MAPK family.
Antrodia cinnamomea (formerly A. camphorata) has recently and commercially been used in the formulation of nutraceuticals and functional foods in Taiwan. Because of its diverse properties, the neuroprotective effect was investigated using a fermented A. cinnamomea extract in this study. Serum deprivation-induced apoptosis in neuronal-like pheochromocytoma (PC12) cells was used as a cell stress model, and it was found that A. cinnamomea was effective in preventing serum-deprived apoptosis according to results of an MTT assay and Hoechst staining. Serum deprivation resulted in decreased phosphorylation of extracellular signal-regulated kinase (ERK) and increased phosphorylations of c-Jun NH2-terminal kinase (JNK) and p38, of the family of mitogen-activated protein kinases (MAPKs); however, A. cinnamomea reversed these phenomena, supporting the antagonistic effects between ERK and JNK-p38 in regulating cell survival. The previously identified active component of A. cinnamomea, adenosine (ADO), also exerted the same effects as A. cinnamomea in preventing apoptosis and regulating phosphorylations of MAPKs. Although an inhibitor of the ERK upstream activator blocked A. cinnamomea-induced ERK phosphorylations, it failed to block the protection of A. cinnamomea and ADO. A protein kinase A (PKA) inhibitor blocked the protection by both A. cinnamomea and ADO. Both JNK and p38 inhibitors were effective in preventing the phosphorylations of JNK and p38 and serum deprivation-induced apoptosis. Collectively, A. cinnamomea prevented serum deprivation-induced PC12 cell apoptosis through a PKA-dependent pathway and by suppression of JNK and p38 activities.
Lu
Mei-Kuang
MK
National Research Institute of Chinese Medicine, 155-1 Li-Nung Street, Sec. 2, Shipai, Peitou, Taipei 112, Taiwan.
Cheng
Jing-Jy
JJ
Lai
Wen-Lin
WL
Lin
Yen-Ju
YJ
Huang
Nai-Kuei
NK
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D005285:Fermentation; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D020072:Polyporales / Q000737:chemistry*; D051381:Rats
D016895:Culture Media, Serum-Free; D018696:Neuroprotective Agents; D020928:Mitogen-Activated Protein Kinases; D000241:Adenosine