Hypoxia and reoxygenation increased BACE1 mRNA and protein levels in human neuroblastoma SH-SY5Y cells.
Ischemic cerebrovascular diseases, usually involved in hypoxia and reoxygenation, have been reported to increase the risk of dementia such as Alzheimer's disease (AD). beta-site amyloid protein precursor (APP)-cleaving enzymes (BACE1) have been identified to participate in the secretion of beta-amyloid peptides (Abeta), and its expressive alteration would contribute to the AD neuropathology. We have investigated the effect of hypoxia (0% O(2), 24h) and reoxygenation (0h, 12h and 24h after 24h hypoxia) on BACE1 mRNA and protein levels in human neuroblastoma SH-SY5Y cells. At the same time, we also examined the effect of hypoxia and reoxygenation on APP mRNA and protein levels. We demonstrated that hypoxia and reoxygenation did not alter APP mRNA and protein level, However compared to those of controls, BACE1 mRNA levels were up-regulated by 31.5% (P=0.028) and 35.1% (P=0.005) at 12h and 24h and the protein levels increased to 22%(P=0.021), 42% (P=0.000) and 51.5% (P=0.000) at 0h, 12h and 24h after reoxygenation, respectively. Thus by up-regulating of BACE1 mRNA and protein level in the neuronal cell, hypoxia may be a linkage in the pathophysiology between cerebravascular diseases and AD.
Xue
Sufang
S
Department of Neurology, Xuanwu Hospital of the Capital University of Medical Sciences, Neurodegenerative Lab of Ministry of Education of the People's Republic of China, Beijing 100053, China.
Jia
Longfei
L
Jia
Jianping
J
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma; D010100:Oxygen / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D010100:Oxygen