Objective To investigate the expression of amyloid beta precursor-like protein 1 （APLP 1） gene on the transcription level in hippocampus of pilocarpine-induced epileptic rats. Methods Epileptic rats were developed b...Objective To investigate the expression of amyloid beta precursor-like protein 1 （APLP 1） gene on the transcription level in hippocampus of pilocarpine-induced epileptic rats. Methods Epileptic rats were developed by LiCl （3 mmol/kg, i.p.） approximately 20 h prior to pilocarpine （30 mg/kg, i.p.） administration. The 3＇ end partial sequence of rat APLP1 gene was cloned, and the expression levels of APLP1 mRNA in hippocampus of epileptic rats at 6 h, 30 h, 7 d and 15 d were determined by semi-quantitative RT-PCR. Results The 3＇ end partial sequence of rat APLP1 gene shared a 97% homology with that of mice, and 90% with that of human. The APLP1 amino acid sequence of rat was identical with that of mouse, but was different from that of human in 3 residues. Moreover, pilocarpine induced a significant down-regulation ofAPLP1 mRNA expression at 6 h after epilepsy initiation （P 〈 0.05）, and at 30 h, this down-regulation became more dramatic （P 〈 0.01）, which lasted till day 15 （P 〈 0.01）. Conclusion The 3＇ end ofAPLP1 gene is highly conserved, and APLP1 mRNA expression is kept at low level in hippocampus of pilocarpine-induced epileptic rats.展开更多
Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion a...Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion and proliferation.Previously it was thought that autophagy is a novel beta-amyloid peptide(Aβ)-generating pathway activated in AD.However,the protein proteolysis of APLP1 is still largely unknown.The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses,such as proteasome inhibition.Activation of the endoplasmic reticulum(ER)stress by proteasome inhibitors induces autophagy,causing reduction of mature APLP1/APP.Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1.Therefore,our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.展开更多
基金supported by the National Basic Research Development Program of China (No.2006CB504501)National Key Laboratory of Modern Communication Foundation of China (9140C1101050701)the National Natural Sciences Foundation of China (No.30525030)
文摘Objective To investigate the expression of amyloid beta precursor-like protein 1 （APLP 1） gene on the transcription level in hippocampus of pilocarpine-induced epileptic rats. Methods Epileptic rats were developed by LiCl （3 mmol/kg, i.p.） approximately 20 h prior to pilocarpine （30 mg/kg, i.p.） administration. The 3＇ end partial sequence of rat APLP1 gene was cloned, and the expression levels of APLP1 mRNA in hippocampus of epileptic rats at 6 h, 30 h, 7 d and 15 d were determined by semi-quantitative RT-PCR. Results The 3＇ end partial sequence of rat APLP1 gene shared a 97% homology with that of mice, and 90% with that of human. The APLP1 amino acid sequence of rat was identical with that of mouse, but was different from that of human in 3 residues. Moreover, pilocarpine induced a significant down-regulation ofAPLP1 mRNA expression at 6 h after epilepsy initiation （P 〈 0.05）, and at 30 h, this down-regulation became more dramatic （P 〈 0.01）, which lasted till day 15 （P 〈 0.01）. Conclusion The 3＇ end ofAPLP1 gene is highly conserved, and APLP1 mRNA expression is kept at low level in hippocampus of pilocarpine-induced epileptic rats.
基金supported by National Natural Science Foundation of China(Grant No.30900748).
文摘Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion and proliferation.Previously it was thought that autophagy is a novel beta-amyloid peptide(Aβ)-generating pathway activated in AD.However,the protein proteolysis of APLP1 is still largely unknown.The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses,such as proteasome inhibition.Activation of the endoplasmic reticulum(ER)stress by proteasome inhibitors induces autophagy,causing reduction of mature APLP1/APP.Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1.Therefore,our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.
