Li-bin Zhan1, Xin-ping Niu, Hua Sui, Xiao-yang Gong. 1. Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China. libinzhan@hotmail.com
Abstract
OBJECTIVE: To observe the relationship among amyloid beta-peptide (Abeta)-induced neurotoxicity, serum-inducible kinase (SNK)-spine-associated Rap guanosine triphosphatase activating protein (SPAR) pathway and N-methyl-D-aspartate receptor (NMDAR), and to explore the mechanism of the protective effect of spleen-yin nourishing recipe (Zibu Piyin Recipe, ZBPYR) in hippocampal neurons against Abeta-induced neurotoxicity. METHODS: The Abeta(1-40) powder was dissolved in 1 x PBS and incubated at 37 degrees centigrade, and then aggregated fibrillar Abeta(1-40) was obtained 72 h later. We used rat primary hippocampal neurons as cell model. ZBPYR-containing serum was gained by the method of serum pharmacology. ZBPYR-containing serum was added to the culture 1 h before Abeta(1-40) (5 micromol/L) exposure. Cells were harvested 2 h after Abeta(1-40) exposure for total RNA extracting. Then the mRNA expression levels of SNK, SPAR and NMDAR subunits NR1, NR2A and NR2B were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After 2-hour Abeta(1-40) exposure, we found that the expression level of SNK mRNA was up-regulated and the expression levels of SPAR, NR1, NR2A and NR2B mRNAs were down-regulated in hippocampal neurons as compared with control group (P < 0.01, P < 0.05). While with ZBPYR-containing serum pretreatment, the expression level of SNK mRNA was down-regulated and the levels of SPAR, NR1, NR2A and NR2B were up-regulated as compared with Abeta(1-40) exposure, and 2% ZBPYR-containing serum showed the best effect (P < 0.05). CONCLUSION: Abeta-induced neurotoxicity was related to SNK-SPAR pathway and NMDAR; ZBPYR-containing serum can protect neurons from Abeta-induced neurotoxicity, and this protective effect may be performed by regulating the expression of NMDAR and blocking of the SNK-SPAR pathway.
OBJECTIVE: To observe the relationship among amyloid beta-peptide (Abeta)-induced neurotoxicity, serum-inducible kinase (SNK)-spine-associated Rap guanosine triphosphatase activating protein (SPAR) pathway and N-methyl-D-aspartate receptor (NMDAR), and to explore the mechanism of the protective effect of spleen-yin nourishing recipe (Zibu Piyin Recipe, ZBPYR) in hippocampal neurons against Abeta-induced neurotoxicity. METHODS: The Abeta(1-40) powder was dissolved in 1 x PBS and incubated at 37 degrees centigrade, and then aggregated fibrillar Abeta(1-40) was obtained 72 h later. We used rat primary hippocampal neurons as cell model. ZBPYR-containing serum was gained by the method of serum pharmacology. ZBPYR-containing serum was added to the culture 1 h before Abeta(1-40) (5 micromol/L) exposure. Cells were harvested 2 h after Abeta(1-40) exposure for total RNA extracting. Then the mRNA expression levels of SNK, SPAR and NMDAR subunits NR1, NR2A and NR2B were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After 2-hour Abeta(1-40) exposure, we found that the expression level of SNK mRNA was up-regulated and the expression levels of SPAR, NR1, NR2A and NR2B mRNAs were down-regulated in hippocampal neurons as compared with control group (P < 0.01, P < 0.05). While with ZBPYR-containing serum pretreatment, the expression level of SNK mRNA was down-regulated and the levels of SPAR, NR1, NR2A and NR2B were up-regulated as compared with Abeta(1-40) exposure, and 2% ZBPYR-containing serum showed the best effect (P < 0.05). CONCLUSION: Abeta-induced neurotoxicity was related to SNK-SPAR pathway and NMDAR; ZBPYR-containing serum can protect neurons from Abeta-induced neurotoxicity, and this protective effect may be performed by regulating the expression of NMDAR and blocking of the SNK-SPAR pathway.
Authors: X Shi; X G Lu; L B Zhan; X Qi; L N Liang; S Y Hu; Y Yan; S Y Zhao; H Sui; F L Zhang Journal: Diabetologia Date: 2011-04-21 Impact factor: 10.122