GM1 up-regulates Ubiquilin 1 expression in human neuroblastoma cells and rat cortical neurons.
GM1 ganglioside was reported to mediate the amyloid beta-protein (Abeta) secretion and accumulation in the pathogenesis of Alzheimer's disease (AD). The objective of this project was to comprehend the underlying molecular changes related to amyloid beta-protein precursor (APP) processing pathway induced by GM1. Using suppression subtractive hybridisation (SSH), we detected one prominent sequence with increased expression in human neuroblastoma cells that stably transfected with human APP695 cDNA treated with GM1. This transcript has high identity to human Ubiquilin 1 gene. Differential expression was initially confirmed by dot blot hybridization. This result was further authenticated with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Furthermore, using Western blots, we discovered that GM1 stimulated the expression of Ubiquilin 1 in human neuroblastoma cells and rat cortical neurons while other gangliosides Asialo-GM1 and GD1b did not. Ubiquilin 1 is one of the candidate genes of AD, which have been shown to modulate the gamma-secretase components in the proteolytic processing of APP, and is therefore a putative candidate for further investigation of GM1 mechanisms in the etiology and pathology of AD.
Liu
Zhonghua
Z
Department of Biochemistry, Institute of Mental Health, Peking University, Beijing, China.
Ruan
Yanyan
Y
Yue
Weihua
W
Zhu
Zhihui
Z
Hartmann
Tobias
T
Beyreuther
Konrad
K
Zhang
Dai
D
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D009693:Nucleic Acid Hybridization / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C107792:UBQLN1 protein, human; D005677:G(M1) Ganglioside