Oleoylethanolamide attenuates apoptosis by inhibiting the TLR4/NF-κB and ERK1/2 signaling pathways in mice with acute ischemic stroke
- 479 Downloads
This study was carried out to investigate the exact mechanisms behind the neuroprotective effects of oleoylethanolamide (OEA) after acute cerebral ischemic injury. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. OEA (40 mg/kg, ip) was administered with a single injection upon reperfusion. The number of apoptotic cells was detected by TUNEL staining. The expression of Bax, Bcl-2, and TLR4, as well as the activities of NF-κB, Akt, and ERK1/2 were analyzed by western blot. Our data showed that OEA treatment alleviated cell apoptosis in a mouse model of ischemic stroke, accompanied by suppression of Bax, as well as upregulation of antiapoptotic protein Bcl-2 level. The changes of Bax and Bcl-2 could not be observed in PPARα knockout mice models with OEA administration. Importantly, OEA inhibited MCAO-induced TLR4 expression, NF-κB activation, IκBα degradation, and ERK1/2 phosphorylation. Our findings demonstrated that the neuroprotective effects of OEA on cerebral ischemia may be attributed to its antiapoptotic property achieved, at least in part, through the PPARα signaling and inhibition of both TLR4/NF-κB and ERK1/2 signaling pathways. These results provide new evidence indicating the neuroprotective effect of OEA on ischemic stroke.
KeywordsOleoylethanolamide Mice Focal cerebral ischemia Apoptosis
This study was supported by grants from the National Natural Sciences Foundation of China (Nos. 81373407, 81402921, and 81603093), the Natural Science Foundation of Fujian, China (Nos. 2016J01415, 2016D024, and 2015J01354), and the Science and Technology Project of Xiamen, China (No. 3502Z20144027).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Gonzalez-Aparicio R, Blanco E, Serrano A, Pavon FJ, Parsons LH, Maldonado R, Robledo P, Fernandez-Espejo E, De Fonseca FR (2014) The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental parkinsonism. Int J Neuropsychopharmacol 17:455–468CrossRefPubMedGoogle Scholar
- Lan R, Xiang J, Zhang Y, Wang G-H, Bao J, Li W-W, Zhang W, Xu L-L, (2013) Cai D-F (2013) PI3K/Akt pathway contributes to neurovascular unit protection of Xiao-Xu-Ming decoction against focal cerebral ischemia and reperfusion injury in rats. Evid Based Complement Alternat Med 16:1–17Google Scholar
- Lanzillotta A, Porrini V, Bellucci A, Benarese M, Branca C, Parrella E, Spano PF, Pizzi M (2015) NF-κB in innate neuroprotection and age-related neurodegenerative diseases. Front Neurol 6:1–8Google Scholar
- Namura S, Iihara K, Takami S, Nagata I, Kikuchi H, Matsushita K, Moskowitz MA, Bonventre JV, Alessandrini A (2001) Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc Natl Acad Sci 98:11569–11574CrossRefPubMedPubMedCentralGoogle Scholar
- Salakou S, Kardamakis D, Tsamandas AC, Zolota V, Apostolakis E, Tzelepi V, Papathanasopoulos P, Bonikos DS, Papapetropoulos T, Petsas T (2007) Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis. In vivo 21:123–132PubMedGoogle Scholar