Toyomoto Misao, Ohta Mitsuhiro, Okumura Kohji, Yano Hiroe, Matsumoto Kaori, Inoue Seiji, Hayashi Kyozo, Ikeda Kiyoshi
Department of Biochemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan.
FEBS Lett. 2004 Mar 26;562(1-3):211-5. doi: 10.1016/S0014-5793(04)00246-7.
We found that prostaglandin (PG) D(2) and PGE(2), which are major PGs in the brain of mammals, powerfully induced the secretion of nerve growth factor (NGF) from cultured mouse astrocytes; PGE(2) or PGD(2) induced an approximately 12- or 19-fold increase in NGF secretion after a 24-h incubation, respectively. Moreover, it was found that the sequential metabolites of PGD(2), PGJ(2), Delta(12)-PGJ(2), and 15-deoxy-Delta(12,14)-PGJ(2), induced the NGF secretion to the culture medium strikingly (60-98-fold of the control after a 24-h incubation). NGF secretion induced by the J(2) series of PGs was accompanied by the increased expression of NGF mRNA. These PGs also stimulated the secretion/synthesis of brain-derived neurotrophic factor (BDNF). Our findings suggest that PGs play a neuroprotective role by inducing NGF and BDNF production in the central nervous system.
我们发现,前列腺素(PG)D₂和PGE₂是哺乳动物大脑中的主要前列腺素,它们能有力地诱导培养的小鼠星形胶质细胞分泌神经生长因子(NGF);孵育24小时后,PGE₂或PGD₂分别使NGF分泌增加约12倍或19倍。此外,还发现PGD₂的系列代谢产物PGJ₂、Δ¹² - PGJ₂和15 - 脱氧 - Δ¹²,¹⁴ - PGJ₂能显著诱导NGF分泌到培养基中(孵育24小时后是对照组的60 - 98倍)。J₂系列前列腺素诱导的NGF分泌伴随着NGF mRNA表达的增加。这些前列腺素还刺激了脑源性神经营养因子(BDNF)的分泌/合成。我们的研究结果表明,前列腺素通过在中枢神经系统中诱导NGF和BDNF的产生发挥神经保护作用。