[#2006-01] Lion’s Mane Nagai, Kaoru et al Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-dependent Neuronal cell death via protein kinase C pathway

Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-dependent Neuronal cell death via protein kinase C pathway

Kaoru Nagai ^a,*, Akiko Chiba^b, Toru Nishino^a, Takeo Kubota^a, Hirokazu Kawagishi^b,*

^aDepartment of Epigenetic Medicine, Interdisciplinary Graduate School ofMedicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan
^bDepartment of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka 422-8529, Japan

Abstract

In many types of neurodegeneration, neuronal cell death is induced by endoplasmic reticulum (ER) stress. Hence, natural products able to reduce ER stress are candidates for use in the attenuation of neuronal cell death and, hence, in the reduction of the damage, which occurs in neurodegenerative disease. In this study, we investigated ER stress-reducing natural products from an edible mushroom, Lion’s Mane (Hericium erinaceum). As a result of screening by cell viability assay on the protein glycosylation inhibitor tunicamycin-induced (i.e., ER stress-dependent) cell death, we found that dilinoleoyl-phosphatidylethanolamine (DLPE) was one of the molecules effective at reducing ER stress-dependent cell death in the mouse neuroblastoma cell line Neuro2a cells. A purified DLPE, commercially available, also exhibited a reducing effect on this ER stress-dependent cell death. Therefore, we concluded that DLPE has potential as a protective molecule in ER stress-induced cell death. From the structure of DLPE, it was hypothesized that it might activate protein kinase C (PKC). The activity of PKC-ε, a novel-type PKC, was increased by adding DLPE, and PKC-γ a conventional-type PKC, was activated on the coaddition of diolein and DLPE, as shown by in vitro enzyme activity analysis. The protecting activity of DLPE was attenuated in the presence of a PKC inhibitor GF109203X but not completely diminished. Therefore, DLPE can protect neuronal cells from ER stress-induced cell death, at least in part by the PKC pathway.