N-stearoyltyrosine protects primary neurons from Aβ-induced apoptosis through modulating mitogen-activated protein kinase activity.
N-stearoyltyrosine (NsTyr), an anandamide (AEA) analogue is similar to AEA not only structurally but also in terms of biological activity. Since A beta-induced neuronal injury triggers the activation of mitogen-activated protein kinase (MAPK) pathways and the induction or activation of pro- and anti-apoptotic proteins, in the present study we aimed to assess the protective effect of NsTyr against A beta induced neuronal apoptosis. Cell viability and neuronal injury were respectively measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay. Hoechst staining and flow cytometric assessment were used to evaluate cell apoptosis. The anti-apoptotic mechanism involved MAPK phosphorylation and Bcl-2/Bax expression was investigated. The best neuroprotective effect on A beta 25-35-induced neuronal apoptosis was observed in the presence of NsTyr (1 microM). NsTyr exerted anti-apoptotic effect at least partly via activating p-ERK-Bcl-2 but suppressing p-p38-Bax pathways. Moreover a dynamic balance between p-ERK and p-p38 MAPK pathways in NsTyr-induced neuronal protection suggested an interaction between them. Our results indicated the neuroprotective effect of NsTyr on A beta 25-35-induced neuronal injury was at least partly due to anti-apoptosis and raised the possibility that NsTyr might reduce neurodegenerative disorders.
Yang
Z H
ZH
Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
Sun
K
K
Suo
W H
WH
Yao
L Y
LY
Fu
Q
Q
Cui
Y Y
YY
Fu
G H
GH
Chen
H Z
HZ
Lu
Y
Y
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D014443:Tyrosine; C087584:N-stearoyltyrosine